Expression of the breast differentiation antigen NY-BR-1 in a phyllodes tumor of the vulva

We describe a phyllodes tumor of borderline malignancy in the labium majus of a 49-year-old woman. The histogenetic origin of phyllodes tumors in the vulva is controversial. Strong immunoreactivity for NY-BR-1, a novel breast differentiation antigen, was demonstrated within the epithelial components of the phyllodes tumor. A similar expression pattern was observed in mammary-like glands of the vulva. These findings provide further evidence that phyllodes tumors of the vulva might derive from mammary-like glands in the labium majus or from ectopic breast tissu

DNA Cytophotometric Findings in Pheochromocytoma

Fifty adrenalectomy specimens containing normal (n = 3), hyperplastic (n =4), or neoplastic (n = 43) medullary tissue were subjected lo quantitative measurements of DNA content. Of the 43 pheochromocytomas, 16 were neoplasms inherited in the setting of multiple endocrine neoplasia type 2A. Five of 27 sporadic pheochromocytomas followed a malignant clinical course. Follow-up data were available in 25 patients. In normal medulla and adrenomedullary hyperplasia, either diploid or euploid DNA distributions were found. In contrast, 87% (33 of 38) of the benign and all five malignant pheochromocytomas exhibited nondiploid or aneuploid DNA histograms. No differences in DNA content existed between sporadic and hereditary tumors. In contrast to earlier reports, in this study DNA cytophotometry was not suitable to discriminate benign from malignant adrenomedullary tumors. In addition, DNA measurements appeared not to be a useful tool to assess the prognosis of an individual malignant pheochromocytoma

Increased 18F-FDG uptake mimicking thyroid cancer in a patient with Hashimoto's thyroiditis

Abstract.: We report the case of a 68-year-old patient with a known paravertebral malignant schwannoma, sent to us for postoperative staging. A combined whole-body PET/CT scan showed only poor 18F-fluorodeoxyglucose uptake in the region of the primary tumor but distinct increased fluorodeoxyglucose uptake in the left and right thyroid gland. Thyroid sonography showed two hypoechogenic nodules. Ultrasound-guided fine-needle aspiration biopsy of one nodule showed oxyphil transformed cells, compatible with malignancy. Based on these findings, the patient underwent a subtotal thyroidectomy. Histopathology of the specimen revealed a chronic follicular Hashimoto's thyroiditis. This case demonstrates that Hashimoto's thyroiditis can mimic thyroid cancer in PET but also in sonography and fine-needle aspiration biops

Loneliness, Social Isolation and Their Difference: A Cross-Diagnostic Study in Persistent Depressive Disorder and Borderline Personality Disorder

Background: Interpersonal difficulties are a key feature of persistent depressive disorder (PDD) and borderline personality disorder (BPD). Caught in a vicious circle of dysfunctional interpersonal transaction, PDD and BPD patients are at great risk of experiencing prolonged loneliness. Loneliness, in turn, has been associated with the development of mental disorders and chronic illness trajectories. Besides, several factors may contribute to the experience of loneliness across the lifespan, such as social network characteristics, a history of childhood maltreatment (CM), and cognitive-affective biases such as rejection sensitivity (RS). This cross-diagnostic study approached the topic of perceived loneliness by comparing PDD and BPD patients with healthy controls (HC) in its interplay with symptom burden, social network characteristics, RS as well as CM. Method: Thirty-four PDD patients (DSM-5; 15 female, Mage = 38.2, SD = 12.3), 36 BPD patients (DSM-5; 19 female, Mage = 28.8, SD = 9.2), and 70 age- and gender-matched HC were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI; size, diversity, and embeddedness), Beck Depression Inventory (BDI-II), Borderline Symptom List (BSL-23), Childhood Trauma Questionnaire (CTQ), and Rejection Sensitivity Questionnaire (RSQ). Results: Both patient groups reported significantly higher levels of perceived loneliness, symptom severity, and smaller social network characteristics compared to HC. Loneliness was significantly correlated with severity of self-reported clinical symptoms in PDD and at trend level in BPD. Besides, loneliness tended to be related to social network characteristics for all groups except PDD patients. Both PDD and BPD patients showed higher RS as well as CTQ scores than HC. A history of emotional abuse and emotional neglect was associated with loneliness, and this association was mediated by RS as demonstrated by an exploratory mediation analysis. Discussion: Loneliness is highly prevalent in PDD and BPD patients and contributes to the overall symptom burden. Interestingly, loneliness showed an association with prior experiences of CM as well as current RS. We therefore propose a comprehensive model on how intra- und interpersonal aspects may interplay in the dynamics of loneliness in light of CM. Finally, this model may have further implications for psychotherapeutic interventions

Molekulargenetik und Molekularpathologie beim Prostatakarzinom

Beim häufigsten bösartigen Tumor des Mannes, dem Prostatakarzinom, konnten in den letzten Jahren grosse Fortschritte im Bereich der molekularpathologischen Charakterisierung erzielt werden. Diese Erkenntnisse haben entscheidend zur Entwicklung zielgerichteter Therapien in fortgeschrittenen Stadien des Prostatakarzinoms beigetragen. Die molekularpathologischen Ergebnisse geben zudem wichtige Hinweise auf eine mögliche genetische Prädisposition

The clinical spectrum of limb girdle muscular dystrophy. A survey in the Netherlands

A cross-sectional study was performed in the Netherlands to define the clinical characteristics of the various subtypes within the broad and heterogeneous entity of limb girdle muscular dystrophy (LGMD). An attempt was made to include all known cases of LGMD in the Netherlands. Out of the reported 200 patients, 105 who fulfilled strictly defined criteria were included. Forty-nine patients, mostly suffering from dystrophinopathies and facioscapulohumeral muscular dystrophy, appeared to be misdiagnosed. Thirty-four cases were sporadic, 42 patients came from autosomal recessive and 29 from autosomal dominant families. The estimated prevalence of LGMD in the Netherlands was at least 8.1 x 10-6. The clinical features of the autosomal recessive and sporadic cases were indistinguishable from those of the autosomal dominant patients, although half hypertrophy was seen more frequently, and the course of the disease was more severe in autosomal recessive and sporadic cases. The pectoralis, iliopsoas and gluteal muscles, hip adductors and hamstrings were the most affected muscles. Distal muscle involvement occurred late in the course of the disease. Facial weakness was a rare phenomenon. The severity of the clinical picture was correlated with a deteriorating lung function. All autosomal dominantly inherited cases showed a mild course, although in two families life-expectancy was reduced because of concomitant cardiac involvement

How Reliable Is Ki-67 Immunohistochemistry in Grade 2 Breast Carcinomas? A QA Study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas

Assessment of HER2 status in breast cancer: overall positivity rate and accuracy by fluorescence in situ hybridization and immunohistochemistry in a single institution over 12 years: a quality control study

BACKGROUND: The gold standard of HER2 status assessment in breast cancer is still debated. Immunohistochemistry (IHC) and in-situ technology as fluorescent-labeled methodology (FISH) can be influenced by pre-analytical factors, assay-conditions and interpretation of test results. We retrospectively conducted this quality control study and analyzed HER2 test results in breast cancer within the routine diagnostic service in a single institution over a period of 12 years. We addressed the question how stable and concordant IHC and FISH methods are and whether HER2 positivity rate has changed over this period. METHODS: Data of 7714 consecutive HER2-FISH-assays in a period of 12 years (2001-2012) on breast cancer biopsies and excision specimens were retrospectively analyzed. From 2001 to 2004, FISH tests were performed from all cases with IHC score 3+ and 2+ (and in some tumors with IHC score 1+ and 0). From 2005-2010, HER2 status was only determined by FISH. From 2011-2012, all breast carcinomas were analyzed by both IHC and FISH. Scoring and cut-off-definition were done according to time-current ASCO-CAP and FDA-guidelines. RESULTS: Between 2001-2004, IHC score 3+ was diagnosed in 22% of cases, 69% of these 3+ cases were amplified by FISH. 6% of IHC score 0/1+ cases were amplified by FISH. There was a mean amplification rate of 15.8% (range 13 -19%) using FISH only HER2-assays (2005-2010). Starting 2008, a slight drop in the amplification rate from 17% to 14% was noticed due to the modified ASCO-criteria in 2007. From 2011-2012, 12% of cases were 3+ by IHC, 84% of them were amplified by FISH. Less than 1% of IHC score 0/1+ cases were amplified by FISH. Concordance between FISH and IHC increased from 83% to 97%. CONCLUSIONS: Our quality control study demonstrates that HER2 positivity rate remained stable by FISH-technology but showed a significant variation by IHC over the analyzed 12 years. Improvement in concordance rate was due to standardization of pre-analytical factors, scoring and interpretation

Fatal herpes simplex virus hepatitis in a patient with esophageal cancer under radiochemotherapy

BACKGROUND: Herpes simplex virus (HSV) infections are frequent. However, HSV hepatitis is rare and may lead to a life-threatening condition. CASE REPORT: A 68-year-old patient with a locally advanced and inoperable esophageal carcinoma was treated with induction chemotherapy and combined chemoradiation. After a total of 9 weeks of treatment, he developed fulminant liver failure of unknown origin and died a few days later. Surprisingly, the post mortem examination revealed an HSV infection of the esophagus and an HSV-associated necrotisizing hepatitis. CONCLUSION: In this immunocompromised patient, we postulate an HSV-associated esophagitis that led to viremia and fulminant hepatitis. Especially in immunocompromised hosts, HSV hepatitis should be considered in the differential diagnosis in patients with anicteric hepatitis and marked elevation of transaminases. A liver biopsy is the quickest and most definitive diagnostic tool to diagnose HSV hepatitis. If this is not possible because of severe coagulopathy, polymerase chain reaction for HSV DNA should be performed. Awaiting diagnosis, a prompt empirical treatment with acyclovir has to be discussed in case of a characteristic biochemical profile