Patients with neuregulin 1 (NRG1) rearranged cancer are suitable for the theranostic approach and targeted therapy.

INTRODUCTION: Neuregulin 1 (NRG1) gene fusion was detected in a wide range of carcinomas. It is most frequently present in lung adenocarcinomas, especially in KRAS and BRAF wild-type cases. PURPOSE: We present a newly described diverse group of NRG1 rearranged carcinomas. The paper explains basic molecular principles associated with this oncogenic driver. It consists of ERBB3 (HER3) and ERBB2 (HER2) receptor activation with downstream activation of PIK and MAPK canonical pathways. The experience with new therapeutic modalities is summarized. CONCLUSIONS: So far, the global results of cytotoxic, immune and targeted therapies were dis-appointing. Further research (including two studies in Europe) is underway, developing new therapeutic strategies and examining this cancer bio-logy. In the meantime, it is possible to dia-gnose NRG1 rearranged carcinomas in the Czech Republic since mRNA next generation sequencing (NGS) analysis is readily available.

Significance of bizarre cells in cervical screening liquid-based cytology: A prospective study of 15 cases.

OBJECTIVE: The aim of this study was to assess the significance of bizarre cells (cells of squamous origin with a superficial squamous cell-type cytoplasm and characterised by multinucleation that produces bizarre nuclear shapes) in liquid-based cytology (LBC) Papanicoaou (pap) smears with clinical and histological follow-up correlation. METHODS: Fifteen patients, all with LBC samples containing bizarre cells, were identified in routine ThinPrep® LBC workload. HPV testing was performed in each case using residual LBC material. Cytological-histological correlations were reviewed. RESULTS: All 15 LBC samples contained bizarre cells and tested positive for high-risk HPV types. Ten of the 15 cases were identified as atypical squamous cells - cannot exclude an HSIL (ASC-H) with secondary diagnosis of low-grade squamous intraepithelial lesion (LSIL), while five cases were identified as high-grade squamous intraepithelial lesion (HSIL), and a subsequent biopsy was recommended. Additionally, 13/15 cases underwent cone biopsy or hysterectomy within 1-11 months, of which 10 showed histologically confirmed HSIL end-points. LSIL was present in three cases. Bizarre cells were identified in the HSIL epithelium of five cone biopsies. CONCLUSIONS: Identification of bizarre cells in LBC is straightforward and may facilitate diagnosis. The cytology of bizarre cells is associated with HSIL in cone biopsies. We recommend assigning LBC samples containing bizarre cells as ASC-H with secondary diagnosis of LSIL.

Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a non-endemic eastern european population.

Nasopharyngeal carcinoma (NPC) is a rare malignancy in the Czech Republic and Slovakia, with the standardized incidence rate of < 1:100000 person-years. Viral status of NPC in these non-endemic Eastern European regions is currently unknown. In a retrospective study, we evaluated the presence of EBV and HPV in 62 NPC cases. EBV status was determined by the use of in situ hybridization (ISH) for EBV encoded small RNA 1 (EBER1). HPV status was examined with p16 immunohistochemistry, DNA ISH and DNA polymerase chain reaction. Sixty-one studied cases showed non-keratinizing morphology and one was keratinizing squamous cell carcinoma. Only one NPC with non-keratinizing morphology was scored as p16-positive (nuclear and cytoplasmic staining ≥ 70% of tumor cells). This case was positive for high-risk HPV by ISH and the DNA PCR confirmed the presence of HPV18 type. At the same time, this case was found negative for EBV. Remaining sixty-one cases that were scored as p16-negative were all found HPV-negative by ISH and the DNA PCR. EBV was detected in 85.5% (53/62) of cases and 9 cases were EBV-negative, including the case of keratinizing NPC. In contrast with previous reports on the prevalence of EBV-positivity in Caucasian patients with NPC, the majority of patients coming from this non-endemic region show EBV-positivity; therefore, they may be candidates for novel EBV-targeting therapies. Conversely, HPV-positive NPC is very rare and HPV does not seem to play a significant role in the etiopathogenesis of NPC in these Eastern European populations.

[Spindle cell and cuboidal renal cell carcinoma (loopoma). 10 case reports]. / Vretenobunecný a kuboidální renální karcinom (loopom). Popis 13 prípadu.

BACKGROUND: Current classification systems of neoplasms arising from renal parenchyma distinguish 5 categories of renal cell carcinoma (RCC), i.e. conventional RCC, papillary RCC, chromophobe RCC, collecting duct/medullary RCC and unclassified RCC. We present 13 cases of unusual and unclassified spindle and cuboidal renal cell carcinomas. METHODS AND RESULTS: The studied group consisted of 13 patients (7 men and 6 women). They ranged in age from 22 to 65 years (mean 57.3). Generally, the tumours were well circumscribed and confined to the kidney, whitish to grey on section with a diameter 4.5-13 cm (mean 8.6 cm). One patient was investigated for loin pain and nocturia. Three patients had staghorn nephrolithiasis and vague sonographic findings in renal parenchyma. In one patient the renal tumour was found when examined on follow-up examination for prostatic adenocarcinoma. None of our patients was known to have elevated levels of parathyroid hormone due to hyperplasia, adenoma or carcinoma of the parathyroid gland. Clinical follow-up of the patients ranged from 9 months to 8 years (mean 2.3 years). Microscopically, the tumours were composed of two main populations of cells: flattened, spindle cells with sparse cytoplasm and small cuboidal cells with clear to light eosinophilic cytoplasm. Eight patients are currently well without signs of recurrence or metastasis, one had metastasis in the regional lymph node at the time of nephrectomy, one died of unrelated cause, and three were lost to follow-up. CONCLUSIONS: We present 13 cases of unclassified RCC. Our cases were histologically, immunohistochemically and ultrastructurally similar to the hitherto reported case reports of this variant of RCC. It is obvious, that that variant of RCC should be recognised as a new subtype of RCC.

Spindle and cuboidal renal cell carcinoma, a tumour having frequent association with nephrolithiasis: report of 11 cases including a case with hybrid conventional renal cell carcinoma/ spindle and cuboidal renal cell carcinoma components.

AIMS: We present the largest series of an unclassified subtype of renal cell carcinoma, which seems to be a distinct morphological entity and which is sometimes designated as spindle and cuboidal renal cell carcinoma. METHODS AND RESULTS: Eleven cases of spindle and cuboidal renal cell carcinoma were found among 7000 primary renal cell tumours in Pilsen's routine and consultation files. The patients were five men and six women. They ranged in age from 22 to 65 years (mean 56.8). Microscopically, the tumours were composed of two main populations of cells. First, the preponderant type of cells was formed by flattened, spindle cells with sparse cytoplasm. The second cell type was a small cuboidal cell with clear to light eosinophilic cytoplasm. Spindle-shaped cells were arranged in a fascicular pattern often reminiscent of low-grade smooth muscle tumours. Solid areas of spindle cells were also present. Small cuboidal cells formed sparse tubular structures lined by a row of single cells. In addition to all previous published cases of spindle and cuboidal renal cell carcinoma we observed an association of nephrolithiasis in our cases. It was seen in 3/11 of our patients. A previously unreported feature is the occurrence of a conventional renal cell carcinoma component in one of our cases. Seven of our patients are currently well without signs of recurrence or metastasis, one had metastasis in a regional lymph node at the time of nephrectomy, one died of an unrelated condition, and two were lost to follow-up. CONCLUSIONS: We present 11 cases of spindle and cuboidal renal cell carcinoma, which is believed to be a distinctive morphological entity. Our cases were histologically, immunohistochemically and ultrastructurally similar to the previously reported cases of spindle and cuboidal renal cell carcinoma. In contrast to all previously reported cases of spindle and cuboidal renal cell carcinoma, we observed an association with nephrolithiasis in three of our cases; moreover, one of our tumours had a conventional renal cell carcinoma component and another revealed a metastatic focus in a regional lymph node. None of our patients died of the disease. This study confirms that spindle and cuboidal renal cell carcinoma has a low malignant potential.

[Effect of passive leg lifting on sodium excretion in patients with liver cirrhosis]. / Vplyv pasivneho zdvihnutia dolnych koncatin na exkreciu sodika u chorych s cirhozou pecene.

18 healthy subjects and 15 patients with liver cirrhosis were examined using a 2-hour method of passive leg rising (PLR). Renal and hormonal responses to PLR were investigated. There was a significant increase in diuresis (p < 0.01) and sodium excretion (p < 0.01) simultaneously with a decrease in plasma renin activity (p < 0.01) and plasma aldosterone (p < 0.01) in the group of healthy subjects. Similarly, in the group of patients with liver cirrhosis a significant increase in diuresis (p < 0.01), natriuresis (p < 0.05) together with a decrease in plasma renin activity (p < 0.05) and aldosterone (p < 0.01) were detected. 3 of 15 patients were nonrespondents. We conclude that PLR leads to central volume expansion which causes suppression of sodium retaining factors, and the increase in diuresis and natriuresis not only in healthy objects but also in cirrhotics. This simple method may be used as the first therapeutic regimen in patients with cirrhosis and edemas. (Tab. 2, Fig. 3, Ref. 13.)

A study of the renal sodium excretion during the normal menstrual cycle using method of passive leg rising.

12 healthy women (age 18-38 years) were examined using the 2-hour's method of passive leg rising (PLR) in follicular (FP) and luteal (LP) phases of normal ovulatory cycle. Renal and hormonal response to PLR was investigated. There was a significant increase of diuresis (from 53 +/- 9 ml/h to 298 +/- 27 ml/h in FP, from 69 +/- 12 to 324 +/- 28 ml/h in LP) and natriuresis (from 4.5 +/- 0.9 to 9.8 +/- 1 mmol/h in FP, from 5.7 +/- 0.3 to 12.1 +/- 1.1 mmol/h in LP), simultaneously with a decrease of plasma renin activity (PRA) and plasma aldosterone (PA) in both FP and LP. Baseline PRA was mildly and PA was significantly higher in LP compared to FP. Urinary osmolarity, heart rate and systolic blood pressure dropped significantly. Renal and hormonal response to PLR were identical in the two phases of the menstrual cycle. Authors conclude that 1/PLR causes significant diuresis and natriuresis due to central volume expansion and may be used as a simple stimulating test of renal sodium excretion, 2/renal sodium retention does not occur in the LP of normal ovulatory cycle.