Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.

BACKGROUND: Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs. METHODS: The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored. RESULTS: Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively). CONCLUSIONS: LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.

Unnecessary orchiectomy due to atypical sarcoidosis manifesting as a unilateral scrotal mass: a case report and literature review.

Sarcoidosis is a disease characterised primarily by lung tissue involvement. Extrapulmonary involvement, particularly in the genitourinary tract, is extremely rare, particularly when it comes to primary disease detection in this location. The gold standard in establishing a definitive diagnosis of sarcoidosis is a combination of the clinical picture, the results of imaging methods, and histopathological examination from the biopsy taken (thus ruling out other causes of granulomatous inflammation). However, it is common for the biopsy to be infeasible or for the patient to refuse such an examination, resulting in the neglect of this critical verification. We introduce the case of a young 29-year-old man of Czech nationality who had been complaining for some time about non-specific pain above the pubic bone and in the lower abdomen, which was combined with a painless enlargement of the right half of the scrotum. Due to suspected malignancy, it was, after considering clinical, imaging, and laboratory findings, decided to perform a radical orchiectomy as a treatment option. The histological examination revealed that it was not cancer, but rather a rare genitourinary form of extrapulmonary sarcoidosis. In this case, radical resection had been, therefore, unnecessary. We also present a review of the literature on published extrapulmonary, genitourinary, and testicular sarcoidosis cases. All the above demonstrates the importance of considering a possible atypical sarcoidosis manifestation and histological confirmation before pursuing radical solutions.

A unique case of AH-dominant type nodular pulmonary amyloidosis presenting as a spontaneous pneumothorax: a case report and review of the literature.

Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.

Case report: Gaucher disease in trepanobiopsy of 16yo woman examined for suspected myelodysplastic syndrome.

Gaucher disease is an autosomal recessive disease belonging to the so-called storage diseases. More than 300 mutations of the GBA1 gene encoding the β-glucocerebrosidase enzyme are known. It is a very rare disease in the Czech Republic. Currently 35 patients are treated. In our case report, we present the case of a 16 year old female patient attending the Clinic of Pediatric Medicine at the University Hospital in Ostrava. Since 2007, the patient has suffered prolonged thrombocytopenia, at the time with progression, and splenomegaly, which has not been further investigated. Trepanobiopsy was sent to the Department of Pathology with suspicion of myelodysplastic syndrome in May of 2018. In the biopsy examination, the individual bloodline did not show dysplastic features and the number of blasts was not increased. The marrow interstitium was 70% permeated with gaucher cells with intraplasmatic fibrous material. Cells were in the appearance of „crumpled paper“ and expressed CD68 in immunohistochemical stain and in histochemical examination of PAS and iron (Fe) staining. Based on a morphological finding, Gauchers disease was suspected. Repeated bone marrow aspirates were subsequently captured by gaucher cells, and a next biochemical examination showed a β-glucocerebrosidase enzyme decrease of activity. Gaucher disease is a progressive disease that requires early diagnosis with the onset of therapy.

Atypical carcinoma detected after regression of a "benign" oral white lesion. A case report.

BACKGROUND: Unlike leukoplakia, the smokers' lesion - a type of oral white lesion spontaneously regressing following cessation of smoking - is generally considered a non-serious condition and there is no recommendation for subsequent follow-up of such patients. CASE REPORT: Here, however, we present the case of a patient (female, 56, smoker) in whom we detected a smoker's lesion which regressed completely, without any signs of abnormality or malignity. The only shadow of a doubt that led us to inviting her for another examination was an additional examination using a VELscope® autofluorescence device that revealed autofluorescence suppression on the site of the former lesion. Another examination one month later revealed a patch of epithelium with a normal color but a negligibly different light reflection in the center of the former lesion; VELscope® indicated the questionable area to still be suspect. Following excision using margins indicated by VELscope® (+2-3 mm), histopathology revealed a squamous cell carcinoma. The secondary excision was carcinoma free and even after 5 years, the carcinoma has not recurred. CONCLUSION: We would like to point out that apparent spontaneous regressions of oral white lesions following smoking cessation still need attention and close follow-up to make sure that a developing squamous cell carcinoma cannot pass undetected.

The impact of standard protocol implementation on the quality of colorectal cancer pathology reporting.

BACKGROUND: The aim of the study is to assess the influence of standardized protocol implementation on the quality of colorectal cancer histopathology reporting. METHODS: A standardized protocol was created based on the recommendations of The College of American Pathologists. The impact of this protocol was measured by comparing frequencies of assessed parameters in histopathology reports before and after implementation. RESULTS: In total, 177 histopathology reports were included in this study. The numbers of harvested lymph nodes were 12.4 ± 5.2 (colon) and 12.6 ± 5.4 (rectum) before protocol; and 17.1 ± 6.5 (colon), and 16.6 ± 7.0 after protocol implementation; differences were statistically significant. The recommended minimum of 12 lymph nodes was not achieved in 42.8 % (colon) and 45.7 % (rectum) of specimens before, and in 10.4 % (colon) and 17.7 % (rectum) of specimens after protocol implementation; differences were statistically significant. There were no differences in histopathology assessment of proximal and distal resection margins, grading assessment, TNM staging recording, and number of positive findings of microscopic tumor aggressiveness. The findings of tumor budding, tumor satellites, and assessment of microscopic tumor aggressiveness were more frequent after protocol implementation. Histopathology reports of rectal specimens contained assessments of the macroscopic quality of mesorectum, circumferential resection margin, and neoadjuvant therapy effect (if administered) only after protocol introduction. CONCLUSIONS: A standardized protocol is a valuable and effective tool for improving the quality of histopathology reporting. Its implementation is associated with more precise specimen evaluation, higher numbers of harvested lymph nodes, and improved completeness of histopathology reports.

Technical development of a new semispherical radiofrequency bipolar device (RONJA): ex vivo and in vivo studies.

The aim of this study is to inform about the development of a new semispherical surgical instrument for the bipolar multielectrode radiofrequency liver ablation. Present tools are universal; however they have several disadvantages such as ablation of healthy tissue, numerous needle punctures, and, therefore, longer operating procedure. Our newly designed and tested semispherical surgical tool can solve some of these disadvantages. By conducting an in vivo study on a set of 12 pigs, randomly divided into two groups, we have compared efficiency of the newly developed instrument with the commonly used device. Statistical analysis showed that there were no significant differences between the groups. On average, the tested instrument RONJA had shorter ablation time in both liver lobes and reduced the total operating time. The depth of the thermal alteration was on average 4 mm larger using the newly tested instrument. The new radiofrequency method described in this study could be used in open liver surgery for the treatment of small liver malignancies (up to 2 cm) in a single application with the aim of saving healthy liver parenchyma. Further experimental studies are needed to confirm these results before clinical application of the method in the treatment of human liver malignancies.