Tihana Džombeta

Immunohistochemical expression of tumor antigens MAGE-A3/4 and NY-ESO-1 in renal oncocytoma and chromophobe renal cell carcinoma

The distinction between renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), especially the eosinophilic variant, can often be difficult. Our study has documented for the first time the expression of MAGE-A3/4 and NY-ESO-1 cancer testis antigens (CTAs) in these tumors. A total of 35 patients (17 ROs and 18 ChRCCs) were included in the study. Two antibodies were used for immunohistochemical staining: 57B recognizing multiple MAGE-A and D8.38 recognizing NY-ESO-1 CTAs. Fifteen (88.2%) samples of RO stained positively for both MAGE-A3/4 and NY-ESO-1 antigens. Regarding ChRCC, seven (38.9%) stained positively for MAGE-A3/4 and six (33.3%) for NY-ESO-1 antigens. Median MAGE-A3/4 expression was moderately positive in RO and negative in ChRCC. The difference in MAGE-A3/4 expression between two tumor groups was significant (P=0.0013). Median NY-ESO-1 expression was strongly positive in RO and negative in ChRCC. The difference in NY-ESO-1 expression between two tumor groups was also significant (P=0.0008). Our study has shown that RO had a significantly higher expression of both CTAs. However, additional research is needed to clarify their potential diagnostic implications.

Inflammation in Prostatic Hyperplasia and Carcinoma—Basic Scientific Approach

Chronic inflammation is associated with both benign conditions and cancer. Likewise, inflammatory cells are quite common in benign prostatic hyperplasia (BPH) and prostatic tissue harboring cancer. Triggers that activate inflammatory pathways in the prostate remain a subject of argument and are likely to be multifactorial, some of these being bacterial antigens, different chemical irritations, and metabolic disorders. Acute and chronic inflammation in prostate leads to accumulation of immunocompetent cells, mainly T lymphocytes and macrophages, but also neutrophils, eosinophils, and mast cells, depending on the type of offending agent. Inflammatory processes activate hyperproliferative programs resulting in nodules seen in BPH, but are also important in creating suitable microenvironment for cancer growth and progression. Inflammatory cells have mostly been shown to have a protumoral effect such as tumor-associated macrophages, but some cell types such as mast cells have antitumoral effects. This review outlines the recent findings and theories supporting the role of inflammatory responses as drivers of both benign and malignant epithelial processes in the prostate gland.

Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor of the ankle following repeated trauma

To the Editor: Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade sarcoma with predilection for the distal portions of the extremities, first described in 1998 under different names by three independent groups of authors, as ‘inflammatory myxoid tumor of the soft parts with bizarre giant cells’, ‘inflammatory myxohyaline tumor of distal extremities with virocyte or ReedSternberg-like cells’ and ‘acral myxoinflammatory fibroblastic sarcoma’. As the tumor is not entirely restricted to acral sites, the term ‘acral’ was withdrawn from the latter to reach a consensus name. MIFS is characterized by proliferation of low grade atypical spindle cells embedded in myxoid and inflammatory stroma with a proportion of larger cells resembling Reed-Sternberg cells and showing characteristic intranuclear virocyte-like inclusions. To date, there have been very few reports of high grade transformation and metastasis. In 2000, Marshall-Taylor and Fanburg-Smith first reported a distinctive soft tissue proliferation characterized by lipomatous/hemosiderotic spindle cell histology and predilection for the ankle of female patients. ‘Hemosiderotic fibrohistiocytic lipomatous lesion’ was the original name, which was later abbreviated to ‘hemosiderotic fibrolipomatous tumor’ (HFLT). More recently, several studies have demonstrated a consistent t(1;10)(p22;q24) translocation in both tumors, showing evidence for a common origin. Further findings from the few recently reported hybrid HFLT/MIFS cases give evidence that HFLT and MIFS could represent different levels of tumor progression within the same entity. A 57-year-old woman was admitted for treatment of a large soft tissue tumor surrounding the right ankle and extending distally along the foot arch (Fig. 1a). Clinical history showed multiple repeated injuries in the ankle and foot area, which started 40 years prior, when the patient suffered a right ankle fracture. Twelve years later, the patient developed frostbite in the same area. A year later, a tractor spreader drove across the same foot. In 1996, 23 years after the incipient injury, lymphedema of the right foot started to develop. Two years later, the patient spilt boiling water across the foot. In a few days, the patient fell and broke the ankle again. Six years later, the foot was traumatized in a traffic accident. It was only in 2006 that the patient was admitted for treatment of lymphedema. Two tumors measuring 6 × 5 cm and 3 × 5 cm, respectively, were excised from the ankle and foot region and confirmed as lipomas by the pathologist at an external institution. In 2013, the patient underwent another biopsy in our institution because of tumor recurrence, which raised suspicion for high grade liposarcoma. Radiography revealed a multinodular tumor untreatable by local excision, measuring up to 15 cm. PET-CT scan confirmed the finding, and also revealed increased fluorodeoxyglucose (FDG) uptake in an enlarged right inguinal lymph node. The patient underwent transtibial amputation and biopsy of the enlarged lymph node. Six months after amputation, the patient is without signs of recurrence.

Primary osteosarcoma of bladder diverticulum mimicking intradiverticular calculus: a case report

There is a well-documented relationship between urinary bladder diverticula and intradiverticular neoplasms. The great majorities of these tumors are urothelial carcinomas, but may also be of glandular or squamous type. Sarcomas occurring within bladder diverticula are exceptionally rare and highly malignant lesions, with only 20 well documented cases published in the literature to date (including carcinosarcomas). We report a case of osteosarcoma of the bladder diverticulum in a 68-year old man, which clinically mimicked intradiverticular calculus. To our knowledge, this is the second case described in the literature to date, and the first in English literature.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205089355246060.

High Grade T1 Papillary Urothelial Bladder Cancer Shows Prominent Peritumoral Retraction Clefting

Differentiation of noninvasive from invasive papillary urothelial carcinoma can be challenging due to inability of proper orientation and thermal damage of transurethrally obtained material. The aim of this study was to analyze the presence and extent of peritumoral retractions in pT1 compared to pTa papillary urothelial carcinoma. Since peritumoral retractions may result from altered expression profiles of extracellular matrix proteins, we additionally analyzed the expression of matrix metalloproteinase 2 (MMP-2) and interleukin 8 (IL-8) in these tumors. The study comprised 50 noninvasive (pTa) and 50 invasive (pT1) cases of transurethrally obtained primary papillary urothelial carcinomas. The invasive nature of nests showing peritumoral retractions was confirmed immunohistochemically using antibody against collagen IV. Staining for MMP-2 and IL-8 was evaluated semiquantitatively using immunohistochemical staining index, calculated by multiplying the percentage of positive cells and staining intensity. Peritumoral retractions were found in 32% of pT1 carcinomas but in none of the pTa carcinomas. All tumors showing peritumoral retraction were high grade tumors. There was no statistically significant correlation between the expression of MMP-2 or IL-8 and the presence of peritumoral retractions or stage of the tumor (pTa vs. pT1). A statistically significant but weak correlation was found between MMP-2 and IL-8 expression (χ2-test, p=0,015). There was no statistically significant correlation between the presence of peritumoral retractions or MMP-2 expression and tumor recurrence and progression. Our study shows that, in doubtful cases, when differentiating between pTa and pT1 stages of papillary urothelial carcinoma, the presence of peritumoral retractions could favor the diagnosis of invasive neoplasm.

Proteomics profiling of keratocystic odontogenic tumours reveals AIDA as novel biomarker candidate

BACKGROUND Keratocystic odontogenic tumour (KCOT) is a benign, yet aggressive odontogenic tumour. Herein, proteome analysis of KCOT lesions in comparison with control patient-matched tissue unaffected by the disease and with inflammatory odontogenic cysts, namely radicular cysts is presented. METHODS For the proteomics profiling, two complementary proteomics techniques MALDI-MS/MS and LC-ESI-MS/MS were employed. Potential candidate biomarkers were validated by immunohistochemistry. RESULTS More than 43 proteins were found to be differentially expressed or up-regulated in KCOT lesions in comparison with patient-matched unaffected oral mucosa. These proteins bear important biological functions and are involved in cell proliferation, cytoskeletal re-organization, transcription, cellular motility and apoptosis. In particular, a number of differentially expressed proteins participate in autocrine regulation and signalization within JNK and p38 MAPK signalling pathways. CONCLUSIONS Immunohistochemical validation of chosen putative biomarkers revealed axin interaction partner and dorsalization-antagonist (AIDA), known as a protein that blocks activation of JNK signalling pathway, as a differential biomarker for KCOT lesions on an independent cohort of KCOT tissue samples in comparison with most prevalent intra-oseal lesions inflammatory odontogenic cysts.

Congenital brain anomalies and chromosomal aberrations from the Zagreb Collection of human brains

The Zagreb Collection of developing and adult human brains consists of approximately 1,300 brains of fetuses, children and adults that were collected following routine autopsies in the period from 1974 to 2014. The collection comprises brains of different normal developmental stages that may serve for investigation of normal human brain development. Previous studies on this material have led to several important contributions on human cortical development, such as the discovery of the transient fetal subplate zone. The Zagreb Collection, however, also contains approximately 100 brains with different anomalies including chromosomal aberrations such as Down syndrome. We have analyzed all the available material from the Zagreb Collection and identified 44 brains of fetuses and children with Down syndrome, 10 with Patau syndrome, 6 with Edwards syndrome as well as 7 holoprosencephalic, 7 hydrocephalic and 4 microcephalic brains. The largest part of the Collection is available for further research using modern genetic, immunocytochemical and imaging methods, especially magnetic resonance imaging. Furthermore, the histological slides from the Zagreb Collection are currently being digitally scanned and made available as virtual slides to general scientific audience. The Zagreb Collection represents unique and versatile resource for the future study of normal and abnormal human brain development.

Periacinar retraction clefting and d2-40 expression in prostatic adenocarcinoma.

Retraction clefting is known to appear in various types of tumors, but it has only recently been recognized as a specific histological phenomenon. Previously, it was considered merely a laboratory procedure artifact, but lately, there have been some assumptions that peritumoral retractions actually represent lymphatic spaces. In our study, we analyzed neoplastic glands in 52 specimens of prostatic adenocarcinoma. Immunohistochemical analysis was performed using D2-40 antibody, to highlight lymphatic endothelium and thereby differentiate actual lymph vessels or lymphovascular invasion from periacinar retractions. Our results showed that the number of lymph vessels was significantly lower in tumorous tissue compared to adjacent normal prostatic tissue. On the other hand, the number of lymph vessels in tumorous tissue was significantly higher than the number of lymph vessels mimicking periacinar retractions. Overall, the number of lymph vessels mimicking periacinar clefts was particularly low. These results are in accordance with our previous studies, which had shown that periacinar clefting appears due to lack of basal cells and stromal changes around tumorous acini. Also, these results support our hypothesis that retractions do not represent lymph vessels but should be considered a distinct entity, which is proven to be helpful both as diagnostic and predictive factor.

Melanotic Neuroectodermal Tumor of Infancy of the Upper Arm: A Case Report

Objective: To present a case of a 6-month-old infant with melanotic neuroectodermal tumor of infancy (MNTI) in the upper arm. Clinical Presentation and Intervention: A 6-month-old female presented with a well-circumscribed lesion of the upper arm at the Childrens Hospital Zagreb. A biopsy was performed and microscopy revealed 2 cell populations consisting of small neuroblastic cells and larger melanin-containing epithelial cells. An excisional biopsy performed 1 month later confirmed the initial diagnosis of MNTI, but the tumor had increased in size since the initial biopsy. After complete surgical excision the patient recovered well with no recurrence. Conclusion: The MNTI located in the upper arm was diagnosed on first biopsy and surgically excised completely. The patient recovered without recurrence in a follow-up of 2.5 years.

Malignant Peripheral Nerve Sheath Tumor of the Inguinum and Angiosarcoma of the Scalp in a Child with Neurofibromatosis Type 1

Benign and malignant tumors are common in the setting of neurofibromatosis type 1 (NF1). Malignant peripheral nerve sheath tumor (MPNST) and angiosarcoma are rare tumors in children and adolescents and mostly occur in young patients in relation to NF1. Both histological types can be present in the same tumor mass in patients with NF1. We present a case of 12.5-year-old girl with NF1 who first presented with MPNST of the right inguinal region and 1.5 years later with unrelated angiosarcoma of the scalp.