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Introduction: The aim of this study was to investigate the prevalence of traumatic experiences and symptoms of posttraumatic stress disorder (PTSD) in treatment-seeking individuals with ongoing substance use disorder (SUD) compared to individuals who have recovered from SUD. Methods: Patients with SUD recruited from the STAYER study (N = 114) underwent an examination of alcohol and drug use, childhood trauma, negative life events and PTSD symptomatology. In this study, only participants with 12-month concurrent polysubstance use was included. Using historical data from the STAYER study, alcohol and drug trajectories were dichotomised as (1) current SUD (current SUD) or (2) recovered from substance use disorder (recovered SUD). Crosstabs and chi-tests were used to measure differences between groups. Results: Childhood maltreatment, traumatic experiences later in life and symptoms of concurrent PTSD were highly prevalent in the study population. We found no significant difference between the current and recovered SUD groups. Recovered women reported a lower prevalence of physical neglect ( p  = 0.031), but a higher prevalence of multiple lifetime traumas ( p  = 0.019) compared to women with current SUD. Both women with current SUD and recovered women reported a significantly higher prevalence of sexual aggression than men ( p < 0.001 and p < 0.001, respectively). In addition, men who have recovered from SUD reported a lower prevalence of PTSD symptoms over cut-off 38 ( p  = 0.017), of re-experiencing ( p  = 0.036) and of avoidance ( p  = 0.015), compared to recovered women. Conclusion: Reported trauma did not differ between persons with current SUD and those who had recovered from SUD. Gender differences discovered in this study indicate the importance of developing individualised and gender-specific treatment models for comorbid PTSD/SUD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient's cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse.Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer., Methods and Analysis: A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25-70 years will provide the same data., Ethics and Dissemination: The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request., Trial Registration Number: NCT04488614., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of the study was to evaluate the sensitivity of dynamic spectral imaging (DSI) colposcopy compared with regular colposcopy for women referred with high-grade cervical cytology., Methods: In a prospective, nonrandomized, multicenter study, we included women referred for colposcopy at hospital gynecology clinics with high-grade cytology. Women were examined using either a regular or DSI colposcope. In both groups, colposcopists located 1 area viewed as most suspicious. In the DSI group, this was done before viewing the DSI map. Subsequently, an area was chosen based on the worst color of the DSI map, and further additional biopsies were taken. All women had 4 cervical biopsies taken, all analyzed separately. The main outcome was sensitivity to find cervical intraepithelial neoplasia grade 2 or worse (CIN2+)., Results: A total of 261 women were examined using DSI colposcopy, and 156 women were examined using regular colposcopy. The sensitivity for finding CIN2+ when using the DSI technology as an adjunctive technology was found to be 82.2% (95% CI = 75.9-87.4), based on an average of 1.4 biopsies. This was corresponding in sensitivity to 2 biopsies taken using regular colposcopy (80.3%; 95% CI = 72.3-86.8). There was no difference in sensitivity for CIN+ between the groups when 3 or more biopsies were taken., Conclusions: We found that the DSI colposcope may help direct biopsy placement; however, the improvement is based on small differences in needed biopsies and the clinical significance of this may be small. Multiple biopsies were still superior., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

Objectives Chronic postoperative pain is prevalent after robot-assisted laparoscopic hysterectomy for endometrial cancer. Preoperative Quantitative Sensory Testing (QST) has been utilized to identify patients at risk of developing chronic postoperative pain after a range of surgical procedures. The aim of this prospective, observational study was to (1) determine the prevalence of chronic postoperative pain, (2) assess selected preoperative risk factors for chronic postoperative pain, and (3) evaluate if preoperative QST profiling could predict the development of chronic postoperative pain following robot-assisted laparoscopic hysterectomy for endometrial cancer. Methods One-hundred and sixty consecutive patients were included and handheld pressure algometry, cuff pressure algometry, temporal summation of pain, conditioned pain modulation, and heat pain thresholds were assessed prior to surgery. Patients were asked to fill out a questionnaire concerning pain in the pre- and post-operative time period six months after surgery. Chronic postoperative pain was defined as persistent, moderate to severe pain (mean visual analogue scale (VAS)≥3) on a daily basis six months after surgery. Results The prevalence of chronic postoperative pain after robot-assisted laparoscopic hysterectomy for endometrial cancer was of 13.6% (95% CI 8.4-20.4%). Patients that would develop chronic postoperative pain had a lower BMI (p=0.032), a higher prevalence of preoperative pelvic pain (p<0.001), preoperative heat pain hyperalgesia (p=0.043) and a higher level of acute postoperative pain (p<0.001) when compared to patients that would not develop chronic postoperative pain. A logistic regression model demonstrated that the presence of preoperative pelvic pain was a significant, independent predictive risk factor for development of chronic postoperative pain (OR=6.62, 95% CI 2.26-19.44), whereas none of the QST parameters could predict postoperative pain. Conclusions Preoperative QST assessment could not predict the development of chronic postoperative pain despite preoperative heat pain hyperalgesia in patients that would develop chronic postoperative pain.

Introduction: One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain., Materials and Methods: The study was designed as a nested case-control study within a cohort of women treated for endometrial cancer with robot-assisted laparoscopic hysterectomy. Twenty-six women with chronic postoperative pain were matched on age and body mass index with fifty-two controls without chronic postoperative pain, and metabolic profiling of preoperatively drawn blood samples from a biobank was performed by means of nuclear magnetic resonance spectroscopy., Results: Nineteen metabolites, including cholesterol, cholesteryl ester, linoleic acid, phospholipids, lipids, and triglycerides had statistically significant higher concentrations in a subgroup of patients who would develop chronic postoperative pain on a later stage compared to the group of patients who would not develop chronic postoperative pain ( p  <   0.05). A sparse Partial Least Squares-Discriminant Analysis model explained 38.1% of the variance and had a predictive accuracy of 73.1%., Conclusions: This explorative study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.

Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival., Methods: The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group., Results: Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth., Conclusions: Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients., Trial of Registration: ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

Purpose: Tamoxifen is an important targeted endocrine therapy in breast cancer. However, side effects and early discontinuation of tamoxifen remains a barrier for obtaining the improved outcome benefits of long-term tamoxifen treatment. Biomarkers predictive of tamoxifen side effects remain unidentified. The objective of this prospective population-based study was to investigate the value of tamoxifen metabolite concentrations as biomarkers for side effects. A second objective was to assess the validity of discontinuation rates obtained through pharmacy records with the use of tamoxifen drug monitoring., Methods: Longitudinal serum samples, patient-reported outcome measures and pharmacy records from 220 breast cancer patients were obtained over a 6-year period. Serum concentrations of tamoxifen metabolites were measured by LC-MS/MS. Associations between metabolite concentrations and side effects were analyzed by logistic regression and cross table analyses. To determine the validity of pharmacy records we compared longitudinal tamoxifen concentrations to discontinuation rates obtained through the Norwegian Prescription database (NorPD). Multivariable Cox regression models were performed to identify predictors of discontinuation., Results: At the 2nd year of follow-up, a significant association between vaginal dryness and high concentrations of tamoxifen, Z-4'-OHtam and tam-NoX was identified. NorPD showed a tamoxifen-discontinuation rate of 17.9% at 5 years and drug monitoring demonstrated similar rates. Nausea, vaginal dryness and chemotherapy-naive status were significant risk factors for tamoxifen discontinuation., Conclusions: This real-world data study suggests that measurements of tamoxifen metabolite concentrations may be predictive of vaginal dryness in breast cancer patients and verifies NorPD as a reliable source of adherence data.

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion., Competing Interests: Conflict of interest: Haukeland University Hospital has patents and pending patent applications on the issue of B cell depletion therapy for myalgic encephalopathy/chronic fatigue syndrome, a treatment principle mentioned in the discussion of the article. Family members of WO2009083602 A1 are pending and some of them are granted, including US 7.914.785. Øystein Fluge and Olav Mella are named as inventors.

Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6-9.5 g/L, IgA 1.8-1.5 g/L, and IgM 0.97-0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B-cell regulatory effects on T-cell or NK-cell subsets are not the main mechanisms for the observed improvements in ME/CFS symptoms observed in the two previous trials. The modest increase in serum BAFF levels at baseline may indicate an activated B-lymphocyte system in a subgroup of ME/CFS patients.

Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a) play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA) reveals that these seven microRNAs interact more readily with estrogen receptor (ER)-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA), suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted.

Background: Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We previously reported a pilot case series followed by a small, randomized, placebo-controlled phase II study, suggesting that B-cell depletion using the monoclonal anti-CD20 antibody rituximab can yield clinical benefit in ME/CFS., Methods: In this single-center, open-label, one-armed phase II study (NCT01156909), 29 patients were included for treatment with rituximab (500 mg/m2) two infusions two weeks apart, followed by maintenance rituximab infusions after 3, 6, 10 and 15 months, and with follow-up for 36 months., Findings: Major or moderate responses, predefined as lasting improvements in self-reported Fatigue score, were detected in 18 out of 29 patients (intention to treat). Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8-66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity., Conclusion: In a subgroup of ME/CFS patients, prolonged B-cell depletion with rituximab maintenance infusions was associated with sustained clinical responses. The observed patterns of delayed responses and relapse after B-cell depletion and regeneration, a three times higher disease prevalence in women than in men, and a previously demonstrated increase in B-cell lymphoma risk for elderly ME/CFS patients, suggest that ME/CFS may be a variant of an autoimmune disease., Trial Registration: ClinicalTrials.gov NCT01156909.

We describe a case of invasive Group A Streptococci infection prior to rupture of the membranes in a 27-year-old woman in her 34th week of pregnancy. The patient's initial symptoms were flu-like with episodes of diarrhoea. After three days she got a fever and was committed to the obstetric ward. After 14 hours of observation she developed abdominal pain with palpatory soreness of the uterus. An acute cesarean section was performed. Group A Streptococci were found in the specimens from the amniotic fluid and placenta.

One third of the pregnant Danish women are overweight or obese. Maternal obesity is an independent risk factor for adverse maternal and foetal outcomes including infertility, miscarriage, congenital malformations, preeclampsia, gestational diabetes, complicated deliveries, caesarean section, macrosomia and childhood obesity. This article reviews the effect of maternal obesity on obstetric and neonatal outcomes and provides recommendations for management of obesity in pregnancy.

Objective: To develop a porcine model for Left Ventricular Hypertrophy (LVH) in which cardiac performance could be quantified non-invasively by Doppler ultrasound., Design: Sixteen 5 kg piglets were divided into two groups. In the first group (n=12) we performed an aortic banding and in the second group (n=4) a sham-operation. Endpoints were echo-assessed left ventricular midseptal and free-wall thickness, heart/body-weight ratio and cardiac myocyte diameter., Results: Free-wall thickness: 0.77+/-0.013 cm in the intervention group and 0.60+/-0.006 cm in the control group (p=0.015). Midseptal thickness: 0.79+/-0.015 cm in the intervention group and 0.58+/-0.010 cm in the control group (p=0.012). Heart/body-weight ratio: 7.73+/-0.970 in the intervention group and 6.23+/-0.430 in the control group (p=0.003). Cardiac myocyte diameter: 19.6+/-4.9 microm in the intervention group and 11.0+/-1.9 microm in the control group (p=0.000)., Conclusion: A chronic porcine model for LVH has been established in which Doppler ultrasound can be used to quantify cardiac function non-invasively.

Simple motor reaction times (RT) in humans show marked trial-to-trial variations. In the present study, a brief tone (400 Hz, 37.5 ms duration) that was the imperative stimulus in a RT paradigm evoked the brainstem frequency-following response (FFR). Horizontal and vertical montage FFRs were recorded to evaluate neural responses with putative origins in auditory nerve and central brainstem, respectively. The main question concerned the possible relationship between trial-to-trial variations in RT speed and FFR response properties. The results showed a reliable pattern in which fast RT trials yielded larger amplitudes (relative to slow trials) in earlier milliseconds of the FFR, and slow RT trials yielded relatively larger amplitudes in later milliseconds of the response. These results support the conclusion that early processing in the auditory brainstem is not automatic and invariant. Rather, short-latency evoked potentials appear to reflect trial-to-trial variations related to events far removed from the first synapse of sensory coding, perhaps depending upon cortically mediated influences such as cognition or attention.

The article reports a case of pseudolymphoma of the stomach. The histological hallmark is lymphoid hyperplasia, with formation of reactive follicles. Most authors believe that this is a benign disorder. The exuberance of the lymphoid reaction may be misinterpreted, however, as malignant lymphoma, which may possibly explain the unduly good prognosis reported in some earlier studies of malignant lymphoma of the stomach.

This report deals with the diagnostic importance of intracytoplasmic lumina. The separation between tubular carcinoma and sclerosing adenosis, and the ultrastructural features of variants of lobular carcinoma are discussed. The role of electron dense granules as well as other markers for neuroendocrine cells are evaluated, and finally, the difficult separation of both small-cell and spindle cell tumors is considered.

Distant metastasis from thymoma is rare. A case with an intraperitoneal metastasis from a thymoma 14 years after removal of the primary tumor is reported. The metastasis was sited in the left hypochondrium and adherent to the spleen, but with no connection to the diaphragm or retroperitoneum. To our knowledge, this location of distant metastasis from thymoma has not been described previously. The malignant potential of thymoma is discussed, and the pattern of reported metastases is summarized.

A fatal rupture of a large paraophthalmic aneurysm 11 months following treatment with detachable balloons is described. This case illustrates the potential consequences of incomplete aneurysm obliteration with endovascular techniques and emphasizes the need for adequate posttreatment evaluation when this method is used for aneurysm therapy.

From 1972 through 1982, 124 patients with muscle invasive T2/T3 bladder carcinoma without evidence of distant metastases were treated with definitive radiotherapy (60 Gy in 6 weeks) to the pelvis at The Norwegian Radium Hospital. Sections from paraffin embedded biopsies taken prior to the start of treatment were prepared for DNA flow cytometry, and 121 histograms were considered interpretable for DNA ploidy values. Significantly improved survival was seen in patients with the following characteristic, univariate analysis: T2 tumor, macroscopically complete removal of the tumor prior to radiotherapy, clinically complete response to radiotherapy, normal serum creatinine, absence of hydronephrosis, tetraploid tumor, WHO performance status 0 or 1, age below 65 years. In a multivariate analysis the following pretreatment variables turned out with prognostic power in this order: normal serum creatinine, T2 tumor, tetraploidy, and absence of small vessel invasion. When including response to therapy, the following factors were significantly predictive of a beneficial survival: clinically complete response after radiotherapy, normal creatinine, T2 tumor and tetraploidy. Tetraploidy was associated with response to radiotherapy when compared to diploid tumors (p = 0.07). This relationship alone did not explain the better survival of patients with tetraploid tumors, and other factors concerned with "tumor aggressivity" may be additional explanatory parameters. DNA ploidy values provide valuable information in the pretreatment situation concerning the prognosis for patients with T2/T3 bladder carcinoma.

Specimens from 7 patients with normal breast tissue 26 patients with benign breast lesions (6 fibroadenomas, and 4 intraductal papillomas, 2 mammae lactantes, 10 cases of cystic disease and 4 fibrotic lesions) were studied by immunocytochemistry and electron microscopy. Excretory epithelial cells in 2 of the 4 papillomas were immunostained for NSE. Myoepithelial cells were frequently stained as well. All the breast specimens were nonreactive to the antichromogranin antibody we used. The 2 NSE positive intraductal papillomas were tested for presence of hormone immunoreactivity, but no positively stained cells were observed. No cells with neuroendocrine features were observed by electron microscopy. The present study did not reveal neuroendocrine cells in the normal breast specimens and undisputed proof of neuroendocrine differentiation in benign breast lesions was not established. We conclude that if neuroendocrine cells are present in the normal breast, they are very rare, and probably not the cellular origin of all breast carcinomas with neuroendocrine features.

Clinical, light microscopic, electron microscopic and immunocytochemical features of 4 cases (3 women and 1 man) of primary malignant fibrous histiocytoma (MFH) of the breast are presented. The literature is reviewed and the diagnosis and treatment discussed. The good outcome is stressed and local excision or simple mastectomy recommended as appropriate treatment.

Protein S-100 immunoreactivity was observed in 5 of 50 breast carcinomas (3 infiltrating lobular and 2 infiltrating ductal carcinomas). A diffuse cytoplasmic staining was present in single cells and groups of cells. The majority of normal myoepithelial cells in ducts of unremarkable appearance next to tumor areas were stained in all 50 breast carcinomas. The 5 protein S-100 positive tumors all stained for prekeratin and 4 of them were vimentin-positive. No immunoreactivity for actin or NSE was observed in the 5 tumors. Electron microscopy did not distinguish the protein S-100 positive carcinomas from the 45 protein S-100 negative tumors. The significance of protein S-100 immunostaining in breast carcinomas is discussed.