MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

[MALIGNANT MELANOMA--THE INFLUENCE OF HORMONAL FACTORS ON THE PROGRESSION AND PROGNOSIS. COMPARATIVE ANALYSIS BASED ON TWO CLINICAL CASES].

Malignant melanoma is the most aggressive form of skin cancer showing extremely high metastatic rate and leading to high levels of lethality. The continually growing incidence of malignant melanoma in the world and his difficult early diagnosis are the occasion for numerous studies. The individual risk for malignant transformation of melanocytes is determined by a number of etiologic factors--endogenous and exogenous. Ultraviolet radiation has a leading role in the group of exogenous factors. Within the group of endogenous factors, besides the well-known photo type skin, as well as genes mutations, are added and the sex hormones, with their significant prognostic importance. The differences, which are observed in the progression and prognosis of malignant melanoma in pre- and postmenopausal women, and men, have defined this cutaneous neoplasma as hormone-dependent tumor. We present two seemingly similar clinical cases of 52 year old woman and 53-year-old man diagnosed with malignant melanomas, developed on the basis of pigmented lesions located on the upper back, as we attempt a comparative analysis on etiopathogenetic factors led to radically different course and prognosis of the disease in these two patients.

[Sebaceous breast carcinoma: report of a rare histological special subtype]. / Sebaziöses Mammakarzinom: Fallbericht eines seltenen speziellen Subtyps.

We report on a case of sebaceous carcinoma of the breast as a rare histological special subtype of breast cancer. Because these tumors are uncommon, differential diagnostic considerations and the exclusion of Muir-Torre syndrome are emphasized. Finally possible mechanisms of development and therapeutic strategies for this carcinoma are discussed.

[Determination of proliferation in breast cancer by immunohistochemical detection of Ki-67]. / Proliferationsbestimmung beim Mammakarzinom durch den immunhistochemischen Nachweis von Ki-67.

Gene expression profiling has demonstrated the prognostic relevance of genes associated with proliferation in breast cancer. The immunohistochemical marker Ki-67 enables routine assessment of proliferation activity in pathology. In a number of retrospective but only few prospective studies the prognostic relevance of Ki-67 in breast cancer could be shown. Although there is no standardized approach with regard to which area of a histological section and how many cells should be counted in a quantitative or semiquantitative fashion as well as to the threshold, Ki-67 is broadly applied in breast pathology. This can be explained by the good reproducibility of the degree of proliferation assessed by Ki-67, at least in the low and high ranges, the possibility to substantiate grading and better practicability in core biopsies in comparison to mitotic counting. In neoadjuvant therapy of hormone receptor positive breast cancer, Ki-67 can probably predict the efficacy of pure hormone receptor blockade without chemotherapy.

[Microviscosity of erythrocyte membranes in breast cancer patients: connection with the receptor phenotype of the tumor].

The state of the viscosity of erythrocyte membranes in breast cancer patients (68--in menopause and 32--with menstrual cycle) was studied in comparison with the content of steroid hormone receptors in the tumor tissue and the age of patients. It is showed that the less hormone dependence of the tumor the higher viscosity of erythrocyte membranes that manifested by a decrease in the coefficient of eximerization (CE) of pyrene in the protein/lipid and in particular, lipid/lipid membrane layers. Increasing CE of pyrene in lipid/lipid layer of erythrocyte membranes above 1.7 units, reflecting a decline in their microviscosity, could be considered as an additional extra-tumor criterion for identification of the tumor as of hormone dependent type.

Emerging treatment options for the management of brain metastases in patients with HER2-positive metastatic breast cancer.

The widespread use of trastuzumab in the past decade has led to a significant and measureable improvement in the survival of patients with human epidermal growth factor receptor-2 (HER2) overexpressing breast cancer, and in many ways has redefined the natural history of this aggressive breast cancer subtype. Historically, survival in patients with HER2-positive disease was dictated by the systemic disease course, and what appears to be the central nervous system (CNS) tropism associated with HER2-amplified tumors was not clinically evident. With improved systemic control and prolonged survival, the incidence of brain metastases has increased, and CNS disease, often in the setting of well-controlled extracranial disease, is proving to be an increasingly important and clinically challenging cause of morbidity and mortality in patients with HER2-positive advanced breast cancer. This review summarizes the known clinical data for the systemic treatment of HER2-positive CNS metastases and includes information about ongoing clinical trials of novel therapies as well as emerging strategies for early detection and prevention.

Imaging of castration-resistant prostrate cancer: development of imaging response biomarkers.

PURPOSE OF REVIEW: The current standard for imaging castration-resistant prostate cancer (CRPC) focuses solely on detection. However, in order to assess treatment response, imaging must provide quantitative results that can be validated. RECENT FINDINGS: Bone scintigraphy remains the most commonly used imaging tool for CRPC in bone, but with limited quantification capabilities. Both PET and MRI provide quantitative measures that could be used to assess treatment response. Several PET tracers have been shown to be able to detect bone metastases, but more research regarding their use for treatment response assessment is necessary. Similarly, research has shown that diffusion-weighted and dynamic contrast-enhanced MRI can detect metastases, with some studies suggesting that they may be suitable for assessing treatment response. SUMMARY: Recent research has shown that many imaging techniques are able to successfully detect metastases in CRPC patients as well as or better than standard imaging. These imaging methods can also be applied to treatment response assessment; however, more research must be done to validate the quantitative measures before these techniques can be used clinically for assessing patients.

[Case report. Aggressive angiomyxoma of vagina. A rare tumor diagnosed]. / Angiomixoma agresivo de vagina: un tumor poco diagnosticado.

The case of a female patient of 35 years of age, with a pedunculated tumor dependent of the vagina, of approximately 25 x 12 x 8 cm, who had a wide resection. The report was consistent with myxoid aggressive angiomyxoma. This is a myxoid mesenchymal neoplasm of slow growth, which mainly appears in deep soft tissues of the pelvic, genital or perineal areas of adult women. It is usually diagnosed after surgical resection by histopathologic examination. Routine evaluation includes: complete physical examination, imaging and pathology report of diagnostic confirmation.

Pulmonary lymphangioleiomyomatosis: literature update.

Pulmonary lymphangioleiomyomatosis is an uncommon disease of unknown etiology characterized by the proliferation of abnormal smooth muscle cells in the lungs, leading to parenchymal destruction and progressive respiratory failure. The natural history of this disease remains poorly understood, primarily seen in women of childbearing age. The diagnosis can be difficult because symptoms are nonspecific and very similar to other respiratory diseases like asthma, emphysema and bronchitis. Lymphangioleiomyomatosis may not be diagnosed until a pneumothorax, chylothorax, interstitial lung disease or angiomyolipomas are discovered. The recent advances in genetic and molecular research provide new hope to discover the intricate mechanism of disease and evaluate new therapies. Internists, primary care physicians and pulmonologists should be aware of this condition in order to avoid delay in the diagnosis and institute appropriate therapy. The clinical features, pathophysiology, molecular genetics and medical treatment will be reviewed.

[Translational research and diagnostics for breast cancer]. / Translationale Forschung und Diagnostik beim Mammakarzinom.

In breast cancer, tumor biological markers are gaining impact and have become equal to traditional markers of pathology. Molecular expression profiling has led to new categories, which by receiving translation into immunohistochemical terms have entered routine pathology use. Besides the triple negative (basal) type, there are hormone receptor positive luminal A and B types and the HER2 type. The distinction between luminal A and B type is not yet clear cut and the proliferation marker Ki-67 as well as diverse RNA expression profiles are used for distinction in order to decide which patients might benefit from pure endocrine and which from combined chemo-endocrine therapy. Prospective studies are necessary to answer these questions. Study data are further awaited to clarify the heterogeneity of triple negative cases which include most of the BRCA1 associated cancers and to elucidate whether within the HER2 category, polysome or pseudopolysome cancer will respond to therapy.

[Urology in 2011]. / Urologie.

In 2011, therapeutic acquisitions in urology allow optimizing management of acute uncomplicated cystitis and acute pyelonephritis by female patients and in men clinical implications of benign prostatic hyperplasia opposed to prostate cancer detection as well as hormonal treatment of advanced prostate cancer.

Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial.

BACKGROUND: A dichotomous index combining two gene expression assays, HOXB13:IL17BR (H:I) and molecular grade index (MGI), was developed to assess risk of recurrence in breast cancer patients. The study objective was to demonstrate the prognostic utility of the combined index in early-stage breast cancer. METHODS: In a blinded retrospective analysis of 588 ER-positive tamoxifen-treated and untreated breast cancer patients from the randomised prospective Stockholm trial, H:I and MGI were measured using real-time RT-PCR. Association with patient outcome was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. A continuous risk index was developed using Cox modelling. RESULTS: The dichotomous H:I+MGI was significantly associated with distant recurrence and breast cancer death. The >50% of tamoxifen-treated patients categorised as low-risk had <3% 10-year distant recurrence risk. A continuous risk model (Breast Cancer Index (BCI)) was developed with the tamoxifen-treated group and the prognostic performance tested in the untreated group was 53% of patients categorised as low risk with an 8.3% 10-year distant recurrence risk. CONCLUSION: Retrospective analysis of this randomised, prospective trial cohort validated the prognostic utility of H:I+MGI and was used to develop and test a continuous risk model that enables prediction of distant recurrence risk at the patient level.

Patterns and incidence of chromosomal instability and their prognostic relevance in breast cancer subtypes.

One of the hallmarks of human solid tumors is chromosomal instability (CIN). We studied global patterns as well as individual levels of CIN and determined the prognostic relevance among breast cancer subtypes. For this, we used single nucleotide polymorphism copy number data of 313 primary lymph-node negative breast cancers. The level of CIN for individual samples was determined by counting the total number of chromosomal segments showing a gain or loss per specimen. Hierarchical clustering resulted in four groups showing distinct patterns of abnormalities, predominantly characterized by 1q gain, 8q gain, 1q&8q gain, or no gain of these loci. Estrogen receptor (ER)-positive and ER-negative samples showed an uneven distribution (statistically significant) across the cluster-groups, as did the molecular subtypes and triple-negative tumors (negative for estrogen-, progesterone-, and her2/neu-receptor). The CIN-score was significantly higher in ER-negative and triple-negative samples. Among luminal cancers, luminal B had a higher CIN-score than luminal A. The CIN-score was significantly associated with prognosis, measured by the time to distant metastasis, in ER-positive, luminal B, and her2/neu subtypes, but not in ER-negative patients. Our study points to a multifaceted role for CIN in breast cancer. Within ER-negative samples, CIN is likely related to the onset but other factors govern the progression of the disease. In contrast, CIN is clearly associated with progression in ER-positive, luminal B, and her2/neu subtypes; thus, assessing CIN in these subtypes may contribute to personalized patient management.

Developing imaging strategies for castration resistant prostate cancer.

Recent advances in the understanding of castrate-resistant prostate cancer (CRPC) have lead to a growing number of experimental therapies, many of which are directed against the androgen-receptor (AR) signaling axis. These advances generate the need for reliable molecular imaging biomarkers to non-invasively determine efficacy, and to better guide treatment selection of these promising AR-targeted drugs. Methods. We draw on our own experience, supplemented by review of the current literature, to discuss the systematic development of imaging biomarkers for use in the context of CRPC, with a focus on bone scintigraphy, F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) and PET imaging of the AR signaling axis. Results. The roadmap to biomarker development mandates rigorous standardization and analytic validation of an assay before it can be qualified successfully for use in an appropriate clinical context. The Prostate Cancer Working Group 2 (PCWG2) criteria for "radiographic" progression by bone scintigraphy serve as a paradigm of this process. Implemented by the Prostate Cancer Clinical Trials Consortium (PCCTC), these consensus criteria may ultimately enable the co-development of more potent and versatile molecular imaging biomarkers. Purported to be superior to single-photon bone scanning, the added value of Na(18)F-PET for imaging of bone metastases is still uncertain. FDG-PET already plays an integral role in the management of many diseases, but requires further evaluation before being qualified in the context of CRPC. PET tracers that probe the AR signaling axis, such as (18)F-FDHT and (89)Zr-591, are now under development as pharmacodynamic markers, and as markers of efficacy, in tandem with FDG-PET. Semi-automated analysis programs for facilitating PET interpretation may serve as a valuable tool to help navigate the biomarker roadmap. Conclusions. Molecular imaging strategies, particularly those that probe the AR signaling axis, have the potential to accelerate drug development in CRPC. The development and use of analytically valid imaging biomarkers will increase the likelihood of clinical qualification, and ultimately lead to improved patient outcomes.

Bilateral segmental neurofibromatosis diagnosed during pregnancy.

Bilateral segmental neurofibromatosis is a rare subtype of neurofibromatosis type 1 defined by lesions affecting a single segment of the body and crossing the midline, with no systemic involvement. We present a case diagnosed during pregnancy because of the characteristic increase in size of the lesions during this period.

[Clinical-laboratory characteristic of adrenal incidentalomas].

Last years while applying modern methods of topic diagnosis the adrenal glands tumors are revealed as an "incidental finding", so called "adrenal incidentalomas" (AI). It is necessary to investigate hormonal activity of these complaints for conduction of timely and radical treatment. The authors have analyzed of complaints, the objective and laboratory investigations data, which were conducted in 122 patients, suffering AI. The tumor hormonal activity identification constitutes one of indications for its surgical treatment.