Bringing pathology to nanomedicine: a comparison of in vivo toxicity of polymeric nanoparticle carriers with and without chitosan coating.

Over the last years, there has been an increasing number of proposals for the use of nanomaterials in medicine. The safety of novel technologies must be verified, prior to their clinical application. Pathology has much to contribute towards this end. In this study, we compared the in vivo toxicity effects of poly- (lactic-co-glycolic acid) nanoparticles with and without chitosan shell. Both nanoparticle types were loaded with curcumin. The nanoparticles were assessed in vitro for potential cytotoxicity with cell viability studies. For the in vivo test, 36 adult Wistar rats were used, four of which were the control group. The remaining 32 were divided into 2 groups, each of which was administered differentially coated drug carriers: (A) nanoparticles without chitosan coating and (B) nanoparticles with chitosan coating. For both groups, the subcutaneous route was used for administration. Each group was further divided into 2 sub-groups of 8 animals each. The animals of the first sub-groups were sacrificed 24 h after the injection and those of the second on the 7th day. The control group was also divided into 2 subgroups of 2 animals each. At the appointed post-administrative date, the rats were sacrificed, and specimens from the brain, liver, kidneys, heart, stomach, lungs, and from the skin at the injection site were collected and studied histopathologically. The evaluation of both in vitro and in vivo testing shows that nanoparticles with chitosan have significantly less, if any, toxic effects compared to those without chitosan.

Solitary Extraskeletal Giant Osteochondroma of the Ankle in a Four-Year-Old Boy.

Solitary extraskeletal osteochondromas are rare benign lesions usually located close to a joint and are characterized by the absence of continuity with the adjacent bone. They are usually found in the hand and feet and are extremely rarely reported in the growing skeleton. In this paper, we describe a four-year-old boy who presented with a solitary calcified tumor in the posterior part of his ankle. We performed a detailed evaluation using plain X-rays, a CT scan, and an MRI, which revealed a well-demarcated calcified tumor that had the characteristics of an osteochondroma but without any continuity with the bones of the ankle joint. The lesion was treated surgically with the excision of a giant osteochondral lesion. Pathological examination revealed mature cartilage at the periphery with cancellous bone in the central part. Thus, we present the clinical and laboratory investigation of a solitary extraskeletal osteochondroma in the ankle of a four-year-old boy, which is an extremely rare case.

Sporadic parathyroid adenoma: an updated review of molecular genetics.

Introduction: Primary HPT (PHPT) is a common disorder, affecting approximately 1% of the general population. Parathyroid adenomas emerge as non-familial sporadic in 90% of cases. The aim of this review is to give a detailed update of molecular genetics of sporadic parathyroid adenoma reported in international literature. Methods: A bibliographic research was conducted in PubMed, Google Scholar, and Scopus. Results: Seventy-eight articles were included in our review. CaSR, MEN1, CCND1/PRAD, CDKI, angiogenic factors like VEGF, FGF, TGFß, and IGF1, and apoptotic factors are important genes in parathyroid adenomas pathogenesis that have been established by several studies. A huge list of proteins is differently expressed in parathyroid adenomas measured by Western Blotting, MALDI/TOF, MS spectrometry, and immunohistochemistry. These proteins take part in several cell processes such as cell metabolism, cytoskeleton structural stability, cell oxidative stress regulation, cell death, transcription, translation, cell connection, and cell signaling transmission, while they can be found over- or underexpressed in abnormal tissues. Conclusion: This review gives a detailed analysis of all reported data on genomics and proteomics of parathyroid adenoma. Further studies should be applied on understanding parathyroid adenoma pathogenesis and introducing new biomarkers for early detection of primary hyperparathyroidism.

Prognostic Significance of Low HER2 Expression in Patients With Early Hormone Receptor Positive Breast Cancer.

BACKGROUND/AIM: A possible role of antibody-drug conjugates against tumors with low HER2-expression, leads to the emergence of a new "low-HER2" classification in breast cancer, encompassing tumors from the hormonal-receptor-positive and the triple-negative subgroups. There is a need for data (clinical trial data and real-world evidence) that will accurately describe this population, the risk of recurrence and the possible benefit of HER2 targeted therapies. PATIENTS AND METHODS: We retrospectively analyzed 949 patients from our Department databases, with hormonal receptor-positive and HER2-negative early breast cancer, for whom detailed data for immunohistochemical HER2-staining could be retrieved. RESULTS: HER2-low expression was detected in 66.6% of patients (472 IHC +1 and 160 IHC +2 and ISH-negative). Lobular, or mixed lobular and ductal cancers had a statistically significantly lower chance of being HER2-low when compared to pure infiltrative ductal carcinomas (53.1% vs. 69.3% respectively). HER2-low status was not prognostic for recurrence-free survival or response to neoadjuvant chemotherapy. There was a non-significant trend for increased risk of recurrence for HER2-low, compared to HER2-0, in patients with lobular or mixed lobular and ductal carcinomas (HR=2.192, 95% CI=0.819-5.912). CONCLUSION: Low expression of HER2 in hormonal receptor-positive early breast cancer does not affect prognosis but may lead to a shorter progression-free-survival in lobular and mixed ductal and lobular cancers. Despite optimal management, a large proportion of hormonal receptor-positive patients will relapse. Targeting HER2 in HER2-low cancers may offer a potential additional treatment strategy to improve survival of this group.

Mesothelioma: A Case in a Diagnostic Timeline and the Efficiency of Robot-Assisted Surgery.

We present a case of a 65-year-old male with a difficulty to diagnose mesothelioma. To be specific, three attempts were made to diagnose the disease, and only with a large sample performed with robot-assisted surgery, our pathologists were able to identify the malignancy. The novelty for our case is mostly based on the timeline of the diagnosis along with the tissue samples where we present the course of the transformation from benign to malignancy. All tissue biopsies were checked by two independent pathologists. Conclusively, diagnosis for small local lesions should be performed with an endoscopic method, video-assisted or robot-assisted.

Axillary Lymph Node Tattooing and Targeted Axillary Dissection in Breast Cancer Patients Who Presented as cN+ Before Neoadjuvant Chemotherapy and Became cN0 After Treatment.

INTRODUCTION: Targeted axillary dissection (TAD) is an alternative to axillary dissection for breast cancer patients who presented as cN+ before neoadjuvant chemotherapy (NAC) and became cN0 after treatment. TAD is defined as the removal of sentinel lymph nodes (SLNs) along with the pre-NAC marked positive nodes. Tattooing is an option to mark positive nodes. In this study we aimed to investigate the identification rate of tattooed nodes during surgery, correspondence between tattooed nodes and SLNs, and difficulties and pitfalls of the method. PATIENTS AND METHODS: In 75 patients who were cN+, with axillary lymph nodes known to have or suspected to have disease were tattooed pre-NAC with a sterile carbon suspension (Spot). After NAC completion all patients became cN0 and underwent TAD as an axillary staging procedure. RESULTS: SLNs were identified successfully in 70 of 75 patients (93.3%). All tattooed nodes were identified successfully intraoperatively in 71 of 75 patients (94.6%). Retrieval of all tattooed nodes in surgical specimens was achieved in 74 patients (98.6%). Correspondence between tattooed nodes and SLNs was observed in 53 of 70 patients (75.3%). In 34 patients (45.3%) the number of pigmented nodes in pathological examination was greater than the number of initially tattooed nodes, indicating the possibility of tattoo ink migration. CONCLUSION: Tattoo of axillary lymph nodes is a feasible, accurate, and low-cost method of positive node marking pre-NAC. Pathological confirmation of black pigment in the lymph nodes excised is not by itself warranty of retrieval of all marked node because of tattoo ink migration from one node to another. Intraoperative identification using visual inspection is essential.

Disseminated tuberculosis: A neglected entity in immunocompromised hemodialysis patients.

End-stage renal disease is considered a factor predisposing to increased risk of tuberculosis with frequent extrapulmonary localization. Although extrapulmonary tuberculosis has been observed for decades, disseminated tuberculosis, a major cause of morbidity and mortality in immunocompromised hosts, remains rather neglected. We report an unusual case of an immunocompromised patient with a late diagnosis and delayed treatment of genitourinary tuberculosis that subsequently led to the diagnosis of vertebral and miliary tuberculosis (disseminating tuberculosis). Therefore, increased awareness is warranted from physicians dealing with hemodialysis patients in order to avoid delays in diagnosis and treatment initiation.

Safety and efficacy of suicide gene therapy with adenosine deaminase 5-fluorocytosine silmutaneously in in vitro cultures of melanoma and retinal cell lines.

Local treatment as a treatment modality is gaining increased general acceptance over time. Novel drugs and methodologies of local administration are being investigated in an effort to achieve disease local control. Suicide gene therapy is a method that has been investigated as a local treatment with simultaneously distant disease control. In our current experiment we purchased HTB-70 (melanoma cell line, derived from metastatic axillary node) and CRL-2302 (human retinal epithelium) were from ATCC LGC Standards and Ancotil(®), 2.5 g/250 ml (1 g/00ml) (5-Flucytosine) MEDA; Pharmaceuticals Ltd. UK. Adenosine Cytosine Deaminase (Ad.CD) was also used in order to convert the pro-drug 5-Flucytosine to the active 5-Fluoracil. Three different concentrations of 5-Flucytosine (5-FC) were administered (0.2ml, 0.8ml and 1.2ml). At indicated time-points (4h, 8h and 24h) cell viability and apoptosis were measured. Our concept was to investigate whether suicide gene therapy with Ad. CD-5-FC could be used with safety and efficiency as a future local treatment for melanoma located in the eye cavity. Indeed, our results indicated that in every 5-FC administration had mild cytotoxicity for the retinal cells, while increased apoptosis was observed for the melanoma cell line.

Hybrid carcinoma of the larynx: a case report (adenoid cystic and adenocarcinoma) and review of the literature.

Introduction. The nonsquamous carcinomas of the larynx are considered rare with the majority of malignant tumors in this area, reaching the rate of 95%, to be squamous cell neoplasms. Case Report. The case refers to a 53-year-old man that presented with symptomatology of motor nerve disease. During the evaluation of the neurologic disease, a subglottic mass of the larynx was revealed accidentally in the imaging examination. Under general anesthesia, we performed direct laryngoscopy and biopsy of the mass. The histopathologic examination revealed a hybrid carcinoma coexistence of two different carcinomas, an adenoid cystic carcinoma and an adenocarcinoma, not otherwise specified with poor differentiation. Regarding the therapeutic plan, the mass was considered inoperable due to its expansion to trachea and the patient received radiotherapy. Conclusions. Both the adenocarcinoma and adenoid cystic carcinoma are extremely rare types of malignant tumors in the larynx. The special interest of the present case is the coexistence of these two rare tumors in the same region of the larynx, being a hybrid tumor of the salivary glands in the larynx, which is the second reported case, based on our systematic literature review.

Papillary thyroid microcarcinoma presenting as lymph node metastasis--a diagnostic challenge: case report and systematic review of literature.

Papillary thyroid microcarcinomas (PTMCs) have an excellent prognosis, although a few may metastasize to cervical lymph nodes. However, an infiltrated palpable neck node without evidence of thyroid disease at presentation is uncommon. We report a patient with PTMC presenting as a solitary lymph node metastasis without evidence of primary thyroid tumor in thyroid imaging and with inconclusive lymph node fine-needle biopsy (FNB) cytology. In our case, node excision and histological examination set the diagnosis and immunocytochemical staining of the FNB specimens verified it. A systematic review of reported similar cases was performed; relevant diagnostic dilemmas were also summarized. The clinical presentation of this type of papillary carcinoma becomes evident at a relatively younger age and affects almost equally the two genders; the enlarged lymph node is almost exclusively ipsilateral to the primary tumor, which may be unifocal or multifocal and is difficult to detect by thyroid imaging modalities. Lymph node FNB cytology, thyroglobulin (Tg) measurement in the washout liquid of the FNB needle, FNB immunocytochemistry and lymph node excision accompanied by histological examination provide a stepwise diagnostic approach. We conclude that PTMC may present as a lymph node metastasis without evidence of a primary thyroid tumor. In such cases, thyroid malignancy should be suspected and, in the presence of negative or non-diagnostic lymph node FNB cytology, measurement of Tg in the fluid aspirate should be performed.

Obstructive ileus due to a giant fibroepithelial polyp of the anus.

Fibroepithelial polyps or hypertrophied anal papillae are essentially skin tags that project up from the dentate line and the junction between the skin and the epithelial lining of the anus. They are usually small in size, but sometimes they become enlarged, causing unexpected medical conditions. An extremely rare case of a giant hypertrophied anal papilla complicated by obstructive ileus is reported. Fibroepithelial anal polyp, despite its size, should be included in the differential diagnosis of a smooth mass located near the anal verge, especially in a patient with a history of chronic anal irritation or infection.