Case Report: A Sudden Thyroid-Related Death of a 15-Year-Old Girl.

A 15-year-old young girl was found dead at home. There were no indications of any intervention or the application of force. On the previous day, she was admitted to hospital because of palpitations, fatigue, a headache, and a swollen neck. During a physical examination, a swollen thyroid gland and tachycardia were found. In the family history, her mother had thyroid disease. According to the laboratory values, she had elevated thyroid hormone levels. After administration of beta-blockers, the patient was discharged and died at home during the night. The parents denounced the hospital for medical malpractice; therefore, a Forensic Autopsy was performed. Based on the available clinical data, the autopsy, histological and toxicological results, the cause of death was stated as multiorgan failure due to disseminated intravascular coagulation (DIC) caused by the autoimmune Graves disease. The forensic assessment of the case does not reveal medical malpractice. Post-mortem diagnoses of thyroid disorders in cases of sudden death can be challenging. However, as the reported case illustrates, the diagnosis could be established after a detailed evaluation of antemortem clinical data, autopsy results, histology, and a toxicological examination.

A combined approach for individualized lymphadenectomy in gastric cancer patients.

Introduction: Gastric cancer ranks as the fifth most common cancer globally. The presence of lymph node metastasis is a significant prognostic factor influencing survival. Postoperative morbidity and nodal staging accuracy are heavily affected by the extent of lymph node dissection. Our study aimed to explore the potential integration of two contemporary methods, sentinel node navigation surgery (SNNS) and the Maruyama Computer Program (MCP), to improve the accuracy of nodal staging. Materials and methods: We conducted a prospective data collection involving patients with gastric adenocarcinoma from 2008 to 2018 at the Department of Surgery, University of Debrecen, Hungary. Data from 100 consecutive patients were collected. The primary and secondary endpoints included evaluating the rate of node-negative patients and the diagnostic accuracy of our combined approach. Results: Sentinel node mapping was successful in 97 out of 100 patients. We found that using the threshold value of the Maruyama Index (MI) ≥ 28, all metastatic stations of sentinel-node-negative patients could be identified. Our method achieved 100% sensitivity and negative predictive value, with a specificity of 60.42% (95% CI = 46.31%-72.98%). Discussion: The combined application of SNNS and MCP has proven to be an effective diagnostic technique in the synergistic approach for identifying metastasis-positive lymph node stations. Despite its limitations, this combination may assist clinicians in customizing lymphadenectomy for gastric cancer patients.

Carbonic Anhydrase IX (CAIX) Expressing Hypoxic Micro-environment Hampers CD8+ Immune Cell Infiltrate in Breast Carcinoma.

BACKGROUND: Hypoxia and necrosis are common features of invasive cancer. The dynamic upregulation of carbonic anhydrase IX (CAIX), triggered by hypoxia-inducible factor 1 (HIF-1) is 1 of the mechanisms supporting cellular adaptation to hypoxia in solid tumors, including breast carcinoma. CAIX activity results in extracellular acidosis and in a profound reorganization of the tumor micro-environment, influencing biological behavior and prognosis. The main focus of our study was to evaluate the mass and distribution of the immune infiltrate, more specifically of CD8+ effector T-cells, in relation with tumoral CAIX expression. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded breast carcinoma sections were analyzed following double immunohistochemical staining for CAIX and CD8. Scanned digital slides were evaluated for both labelings, and CD8-related signal was determined within and outside CAIX-positive tumor areas using the HistoQuant (3DHistech) image analysis software. Statistical analysis was performed using GraphPad Prism software. RESULTS: Of the 34 breast carcinomas, 18 tested partially positive for CAIX. The remaining 16 cases were used as the CAIX-negative control group. Necrotic foci were generally associated with CAIX overexpression, and tumors exhibiting signs of necrosis had a significantly higher rate of relative CAIX expression compared with samples without necrosis (11.47±5.505 vs. without necrosis 3.765±3.5 P-value=0.0216). On the other hand, no statistically significant difference was found when comparing relative CD8+ lymphocyte counts in cases with necrosis as opposed to those where necrosis was absent (134.7±55.7 vs. 97.70±57.25; P value=0.1579). No difference in gross CD8+ T-lymphocyte infiltrate could be measured between CAIX positive and negative samples (98.48±37.32 vs. 95.99±50 P value=0.5928). However, in CAIX-expressing tumors a statistical correlation between the CD8+ T-lymphocyte infiltrate and the extent of CAIX-positive areas was observed. Within the same tumor, CD8+ T-lymphocyte counts showed a significant difference betweeen CAIX+ and CAIX- areas (13.06±9.4 vs. 135.6±62.2 P value <0.0001). CONCLUSION: Our measurements demonstrate for the first time that tumor areas with CAIX expression potentially hamper CD8+ T-lymphocyte infiltration in breast carcinoma. The hypoxia-driven adaptive micro-environment likely interferes with the specific response to biological and immune therapies requiring intact effector T-cell response.

Indolepropionic Acid, a Metabolite of the Microbiome, Has Cytostatic Properties in Breast Cancer by Activating AHR and PXR Receptors and Inducing Oxidative Stress.

Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and animal experiments, we showed that IPA supplementation reduced the proportions of cancer stem cells and the proliferation, movement, and metastasis formation of cancer cells. These were achieved through inhibiting epithelial-to-mesenchymal transition, inducing oxidative and nitrosative stress, and boosting antitumor immune response. Increased oxidative/nitrosative stress was due to the IPA-mediated downregulation of nuclear factor erythroid 2-related factor 2 (NRF2), upregulation of inducible nitric oxide synthase (iNOS), and enhanced mitochondrial reactive species production. Increased oxidative/nitrosative stress led to cytostasis and reductions in cancer cell stem-ness. IPA exerted its effects through aryl hydrocarbon receptor (AHR) and pregnane X receptor (PXR) receptors. A higher expression of PXR and AHR supported better survival in human breast cancer patients, highlighting the importance of IPA-elicited pathways in cytostasis in breast cancer. Furthermore, AHR activation and PXR expression related inversely to cancer cell proliferation level and to the stage and grade of the tumor. The fecal microbiome's capacity for IPA biosynthesis was suppressed in women newly diagnosed with breast cancer, especially with stage 0. Bacterial indole biosynthesis showed correlation with lymphocyte infiltration to tumors in humans. Taken together, we found that IPA is a cytostatic bacterial metabolite, the production of which is suppressed in human breast cancer. Bacterial metabolites, among them, IPA, have a pivotal role in regulating the progression but not the initiation of the disease.

Newborn infants differently process adult directed and infant directed speech.

Infant directed speech (IDS) may serve important functions in language acquisition and in adult-infant communication. The processing of IDS evolves during the first years of life. In order to serve as an effective tool of language acquisition, already very young infants should be able to distinguish IDS from adult directed speech (ADS). We tested whether the ability to discriminate these two speech registers is functional in neonates, by recording EEG from 98 newborn infants in response to Hungarian words naturally spoken in the IDS and the ADS register. Words presented in the ADS register elicited a centro-parietal slow positivity in the 200-600 ms time window whereas words in IDS register elicited a small frontal negativity in the 700-900 ms time window. We conclude that newborn infants differentiate natural speech sounds based on speech register.

[Staphylococcus-induced immunglobulin E-dependent allergic anaphylaxis in Crohn's disease. First description of an association of symptoms]. / Staphylococcus által kiváltott, immunglobulin-E-alapú anafilaxiás reakciók Crohn-betegségben. Egy tünetegyüttes elso leírása.

Immunglobulin E (IgE)-based, irregularly recurring, severe anaphylactic reactions occurred in a 50-year-old European white male patient suffering also from Crohn's disease. On the base of immunologic laboratory tests concerning the mechanism of the phenomenon, the idea arose whether molecules derived for certain microbial derivatives could enter the blood circulation via the damaged bowel walls in the patient with Crohn's disease and they might act as allergens. The microbial analysis diagnosed atypical Staphylococcus in the stool. The serum level of IgE was very high. The concomitant use of targeted antibiotics and anti-allergy and immunosuppressive agents resulted in a complete remission during a couple of months. Not only Crohn's disease has improved, but also the total serum IgE level has decreased significantly, and the unpredictable anaphylactic attacks have been completely eliminated. In Crohn's disease, the anaphylactic complications induced by atypical microbial allergens (e.g., derivatives of Staphylococcus) can be effectively treated after the recognition of this pathological mechanism. This is the first description of such a pathologic state. Orv Hetil. 2019; 160(38): 1514-1518.

[Evaluation of resection margins following breast conserving surgery for breast cancer. A multicentric retrospective study]. / Emlorák miatti szervmegtartó mutétek reszekciós széleinek vizsgálata. Multicentrikus retrospektív elemzés.

Introduction: Breast conserving surgery for breast cancer requires the analysis of surgical margins. If the tumor is not removed completely, additional treatments (reoperation, boost irradiation) are generally recommended. Aim: To analyze the information content of histopathology reports on surgical margins in consecutive cases of breast conservation for invasive female breast cancer, to evaluate the frequency of incompletely removed tumors and to estimate the rate of further treatments after incomplete removal. Method: Analysis of margin related data of consecutive histopathology reports from 8 Hungarian pathology units with locoregional treatment related data in case of unsafe margins. Results: 386 reports were analyzed after exclusions. 200 and 32 cases were identified as having unsafe margins according to the previous (<5 mm) and the new (0 mm) definition of unclear margin, respectively. Unsafe margins were more common with lobular carcinomas. Specimens with clear margins weighed more. Reoperations for unsafe margins were performed in 43/180 and 12/22 cases according to the previous and the new definitions, respectively. Only 75/137 patients without reoperation received boost irradiation of the tumor bed; information on boost radiotherapy was often missing. Residual cancer was identified in 15/43 reoperated patients, of whom 9 had >0 mm margin distance. Conclusions: Some pathology reports lack information on surgical margins. Unsafe margin rates decreased with the new definition. Residual cancer may be left behind in case of clear margins with no ink on tumor. Neither reoperation, nor boost radiotherapy is given to some patients with unclear surgical margins. Orv Hetil. 2019; 160(26): 1036-1044.

[Histological investigation of the walls of lacrimal sacs removed in the course of dacryocystorhinostomy]. / Dacryocystorrhinostomia mutétek során eltávolított könnytömlominták szövettani elemzése.

INTRODUCTION: Endonasal dacryocystorhinostomy (EDCR) has good results. AIM: To perform a prospective histological investigation of the removed lacrimal sacs' walls. METHOD: Between 2016 and 2017, we carried out 21 operations in two groups: inflammatory (11 patients) and non-inflammatory (10 patients) lacrimation groups. The mean age was 60.5 years. Histological samples were investigated after staining them with hematoxylin-eosin. RESULTS: In the non-inflammatory group, histology revealed the incipient metaplasia of the ciliated goblet cells. In the lacrimal sac's wall, there is a chronic inflammation with mucinous metaplasia of the serous glands. In the inflammatory group, the metaplasia of the ciliated goblet cells is more pronounced. Chronic fibrotic inflammation destroys the lacrimal sac's wall, which is dilated, ruptured. The mucinous metaplasia of the serous glands is pronounced. CONCLUSIONS: The results of histological investigations of the lacrimal sacs removed in the course of EDCR are much alike in the inflammatory and non- inflammatory groups. Orv Hetil. 2018; 159(52): 2207-2211.

Comparison of different lymph node staging systems in prognosis of gastric cancer: a bi-institutional study from Hungary.

OBJECTIVE: The Union for International Cancer Control (UICC) Node (N) classification is the most common used staging method for the prognosis of gastric cancer. It demands adequate, at least 16 lymph nodes (LNs) to be dissected; therefore different staging systems were invented. METHODS: Between March 2005 and March 2010, 164 patients were evaluated at the Department of General Surgery in the Kenézy Gyula Hospital and at the Department of General, Thoracic and Vascular Surgery in the Kaposi Mór Hospital. The 6th, 7th and 8th UICC N-staging systems, the number of examined LNs, the number of harvested negative LNs, the metastatic lymph node ratio (MLR) and the log odds of positive LNs (LODDS) were determined to measure their 5-year survival rates and to compare them to each other. RESULTS: The overall 5-year survival rate for all patients was 55.5% with a median overall survival time of 102 months. The tumor stage, gender, UICC N-stages, MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis. The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs. N0 and N3 vs. N0 with multivariate investigation. Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patients and in cases with less than 16 harvested LNs. The MLR gave the best prognostic prediction when adequate (more than or equal to 16) lymphadenectomy was performed. CONCLUSIONS: We suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy.

Large-scale network organization of EEG functional connectivity in newborn infants.

The organization of functional brain networks changes across human lifespan. The present study analyzed functional brain networks in healthy full-term infants (N = 139) within 1-6 days from birth by measuring neural synchrony in EEG recordings during quiet sleep. Large-scale phase synchronization was measured in six frequency bands with the Phase Lag Index. Macroscopic network organization characteristics were quantified by constructing unweighted minimum spanning tree graphs. The cortical networks in early infancy were found to be significantly more hierarchical and had a more cost-efficient organization compared with MST of random control networks, more so in the theta and alpha than in other frequency bands. Frontal and parietal sites acted as the main hubs of these networks, the topological characteristics of which were associated with gestation age (GA). This suggests that individual differences in network topology are related to cortical maturation during the prenatal period, when functional networks shift from strictly centralized toward segregated configurations. Hum Brain Mapp 38:4019-4033, 2017. © 2017 Wiley Periodicals, Inc.

[Role of a computer program in gastric cancer surgery - beyond the evidence]. / A számítógépes program szerepe a gyomortumor-sebészetben ­ Túl az evidencián.

INTRODUCTION: Forty percent of patients with gastric cancer have an unnecessarily extended lymph node dissection with a higher rate of morbidity and mortality. While the Maruyama computer program (MCP) can estimate the lymph node involvement before the surgery, the Maruyama Index (MI) could be a good predictor of overall and disease free survival. METHODS: To measure the probability calculations by MCP, we had to define different "cut-off" levels, with using the calculation of the receiver-operating characteristics analysis. The long term oncological results, as the overall survival (OS) and disease free survival (DFS) were calculated in correlation with the extension of lymphadenectomy (D1 versus D2) and Maruyama Index (MI < 5 versus MI ≥ 5). RESULTS: 74 patients were investigated by the Maruyama computer program preoperatively for the short-term results, and the data of 101 patients were eligible for evaluation of the long-term oncological outcomes. The MCP had a 90.2% of sensitivity, 63.3% of specificity and 78.4% of accuracy. The positive predictive value was 75.5% and the negative predictive value was 84%. In D1 group the DFS was 93.6 months and 68.7 months in D2 group (p = 0.41; HR = 1.34), and the OS was 74.6 and 72.2 months respectively (p = 0.66; HR = 0.87). In patients with MI < 5 the DFS was 92 months and 62.5 months in patients with MI ≥ 5 (p = 0.31; HR = 1.4), while the OS was 86 months and 60.4 months (p = 0.17; HR = 1.52). CONCLUSIONS: Our results proved, that the computerized prediction of LN metastases is efficient and the long term results suggest, that the MI < 5 has a better impact on survival, than the D-level guided surgery.

Clinical significance of lymphadenectomy in patients with gastric cancer.

Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform "low Maruyama Index surgery". The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer.

Mismatch response (MMR) in neonates: Beyond refractoriness.

In the adult auditory system, deviant detection and updating the representation of the environment is reflected by the event-related potential (ERP) component termed the mismatch negativity (MMN). MMN is elicited when a rare-pitch deviant stimulus is presented amongst frequent standard pitch stimuli. The same stimuli also elicit a similar discriminative ERP component in sleeping newborn infants (termed the mismatch response: MMR). Both the MMN and the MMR can be confounded by responses generated by differential refractoriness of frequency-selective neural populations. Employing a stimulus paradigm designed to minimize this confounding effect, newborns were presented with sequences of pure tones under two conditions: In the oddball block, rare deviant tones (500Hz; 10%) were delivered amongst frequent standards (700Hz; 90%). In the control block, a comparison tone (500Hz) was presented with the same probability as the deviant (10%) along with the four contextual tones (700Hz, 980Hz, 1372Hz, 1920.8Hz; 22.5% each). The significant difference found between the response elicited by the deviant and the comparison tone showed that the response elicited by the deviant in the oddball sequences cannot be fully explained by frequency-specific refractoriness of the neural generators. This shows that neonates process sounds in a context-dependent manner as well as strengthens the correspondence between the adult MMN and the infant MMR.

Predictive Factors for Positive Margin and the Surgical Learning Curve in Non-Palpable Breast Cancer After Wire-Guided Localization - Prospective Study of 214 Consecutive Patients.

To investigate the most commonly used technique, the wire-guided localization (WGL) in non-palpable breast cancer. To analyze the effective factors on positive surgical margins in our practice and determine the surgical learning curve of this method. Prospective consecutive study was performed from January 2005 to December 2011. Inclusion criteria was a non-palpable breast lesion with malignancy on preoperative histology. All lesions were localized by ultrasound or stereotactic guided wire placement. Margins 1 mm or closer were accepted as positive margins which required re-excision. To determine the learning curve of WGL method we investigated the change in the reoperation rate after primary procedure performed by "high-volume" surgeon. Two hundred and fourteen consecutive patients were enrolled. In 23 patients (10.7%) reexcision was needed. Positive surgical margins were significantly influenced by the patient's age (p = 0.03), tumor volume (p < =0.001), proportion of tumor volume/specimen volume (p < 0.001), presence of DCIS (p < 0.001), multifocality (p = 0.03) and the learning curve (p = 0.006) with univariate analysis. Only the tumor volume, presence of DCIS and the learning curve were proved as independent prognostic factor for reoperation by multivariate analysis. The reoperation rate decreased below 20% after the fortieth operation. Results of our single institutional study suggest, that this localization technique can be performed safely with very good results after 40 procedures as a learning curve for surgeons.

Processing of Horizontal Sound Localization Cues in Newborn Infants.

OBJECTIVES: By measuring event-related brain potentials (ERPs), the authors tested the sensitivity of the newborn auditory cortex to sound lateralization and to the most common cues of horizontal sound localization. DESIGN: Sixty-eight healthy full-term newborn infants were presented with auditory oddball sequences composed of frequent and rare noise segments in four experimental conditions. The authors tested in them the detection of deviations in the primary cues of sound lateralization (interaural time and level difference) and in actual sound source location (free-field and monaural sound presentation). ERP correlates of deviance detection were measured in two time windows. RESULTS: Deviations in both primary sound localization cues and the ear of stimulation elicited a significant ERP difference in the early (90 to 140 msec) time window. Deviance in actual sound source location (the free-field condition) elicited a significant response in the late (290 to 340 msec) time window. CONCLUSIONS: The early differential response may indicate the detection of a change in the respective auditory features. The authors suggest that the late differential response, which was only elicited by actual sound source location deviation, reflects the detection of location deviance integrating the various cues of sound source location. Although the results suggest that all of the tested binaural cues are processed by the neonatal auditory cortex, utilizing the cues for locating sound sources of these cues may require maturation and learning.

Predictive processing of pitch trends in newborn infants.

The notion of predictive sound processing suggests that the auditory system prepares for upcoming sounds once it has detected regular features within a sequence. Here we investigated whether predictive processes are operating at birth in the human auditory system. Event-related potentials (ERP) were recorded from healthy newborns to occasional ascending pitch steps occurring in the 2nd or the 5th position within trains of tones with otherwise monotonously descending pitch. If the trains were processed in a predictive manner only deviant pitch steps occurring in the later train position would elicit the discriminative mismatch response (MMR). Deviants delivered in the 5th but not in the 2nd position of the tone trains elicited a significant MMR response. These results suggest that newborns represent pitch trends within sound sequences and they process them in a predictive manner. This article is part of a Special Issue entitled SI: Prediction and Attention.

Newborn infants detect cues of concurrent sound segregation.

Separating concurrent sounds is fundamental for a veridical perception of one's auditory surroundings. Sound components that are harmonically related and start at the same time are usually grouped into a common perceptual object, whereas components that are not in harmonic relation or have different onset times are more likely to be perceived in terms of separate objects. Here we tested whether neonates are able to pick up the cues supporting this sound organization principle. We presented newborn infants with a series of complex tones with their harmonics in tune (creating the percept of a unitary sound object) and with manipulated variants, which gave the impression of two concurrently active sound sources. The manipulated variant had either one mistuned partial (single-cue condition) or the onset of this mistuned partial was also delayed (double-cue condition). Tuned and manipulated sounds were presented in random order with equal probabilities. Recording the neonates' electroencephalographic responses allowed us to evaluate their processing of the sounds. Results show that, in both conditions, mistuned sounds elicited a negative displacement of the event-related potential (ERP) relative to tuned sounds from 360 to 400 ms after sound onset. The mistuning-related ERP component resembles the object-related negativity (ORN) component in adults, which is associated with concurrent sound segregation. Delayed onset additionally led to a negative displacement from 160 to 200 ms, which was probably more related to the physical parameters of the sounds than to their perceptual segregation. The elicitation of an ORN-like response in newborn infants suggests that neonates possess the basic capabilities of segregating concurrent sounds by detecting inharmonic relations between the co-occurring sounds.

Detecting the temporal structure of sound sequences in newborn infants.

Most high-level auditory functions require one to detect the onset and offset of sound sequences as well as registering the rate at which sounds are presented within the sound trains. By recording event-related brain potentials to onsets and offsets of tone trains as well as to changes in the presentation rate, we tested whether these fundamental auditory capabilities are functional at birth. Each of these events elicited significant event-related potential components in sleeping healthy neonates. The data thus demonstrate that the newborn brain is sensitive to these acoustic features suggesting that infants are geared towards the temporal aspects of segregating sound sources, speech and music perception already at birth.

Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle.

In this paper, we investigated the isoform-specific roles of certain protein kinase C (PKC) isoforms in the regulation of skeletal muscle growth. Here, we provide the first intriguing functional evidence that nPKCδ (originally described as an inhibitor of proliferation in various cells types) is a key player in promoting both in vitro and in vivo skeletal muscle growth. Recombinant overexpression of a constitutively active nPKCδ in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase-negative mutant of nPKCδ (DN-nPKCδ) markedly inhibited cell growth. Moreover, overexpression of nPKCδ also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient (SCID) mice whereas that of DN-nPKCδ suppressed tumour formation. The role of nPKCδ in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKCδ in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated (PKCα, ß, ε) exerted only minor (mostly growth-inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKCδ as a novel growth-promoting molecule in skeletal muscles and invite further trials to exploit its therapeutic potential in the treatment of skeletal muscle malignancies.

Pleomorphic hyalinizing angiectatic tumor of soft parts: case report with unusual ganglion-like cells and review of the literature.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a recently described, non-metastasizing tumor of uncertain lineage. This tumor distributes equally between the genders and has a predilection for the subcutaneous soft tissue, particularly in lower extremity, other locations are rare. Based on the recent literature, PHAT is suspected to encompass the morphological spectrum with other tumors such as myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT), although cytogenetic data remain inconsistent. We report a case of PHAT that arose in the upper arm with unusual morphology which showed ganglion-like cells similar to Reed-Sternberg-like cells found in MIFS. The tumor had strong immunohistochemical expression of CD34, CD99, and was negative for S-100. The ganglion-like cells were positive for both CD34 and CD68 but negative for CD30. The translocation between chromosome 1 and 10, a frequent finding of MIFS and HFLT, was not identified by FISH excluding the possibility of hybrid PHAT and MIFS. We conclude FISH can be a potential useful tool to separate PHAT with atypical morphology from hybrid tumor in doubted cases. Due to the rarity of PHAT and lack of consistent pathogenetic signatures, more cases and further studies will be needed to elucidate the pathogenesis and nature of this tumor.