Cancer immune profiling unveils biomarkers, immunological pathways, and cell type score associated with glioblastoma patients' survival.

Introduction: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDH wt), and grade 4 astrocytomas, IDH mutant (IDH mut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH wt GBM and IDH mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH wt GBM compared to IDH mut tumors. Regarding IDH wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients' prognosis.

Information theory approaches to improve glioma diagnostic workflows in surgical neuropathology.

AIMS: Resource-strained healthcare ecosystems often struggle with the adoption of the World Health Organization (WHO) recommendations for the classification of central nervous system (CNS) tumors. The generation of robust clinical diagnostic aids and the advancement of simple solutions to inform investment strategies in surgical neuropathology would improve patient care in these settings. METHODS: We used simple information theory calculations on a brain cancer simulation model and real-world data sets to compare contributions of clinical, histologic, immunohistochemical, and molecular information. An image noise assay was generated to compare the efficiencies of different image segmentation methods in H&E and Olig2 stained images obtained from digital slides. An auto-adjustable image analysis workflow was generated and compared with neuropathologists for p53 positivity quantification. Finally, the density of extracted features of the nuclei, p53 positivity quantification, and combined ATRX/age feature was used to generate a predictive model for 1p/19q codeletion in IDH-mutant tumors. RESULTS: Information theory calculations can be performed on open access platforms and provide significant insight into linear and nonlinear associations between diagnostic biomarkers. Age, p53, and ATRX status have significant information for the diagnosis of IDH-mutant tumors. The predictive models may facilitate the reduction of false-positive 1p/19q codeletion by fluorescence in situ hybridization (FISH) testing. CONCLUSIONS: We posit that this approach provides an improvement on the cIMPACT-NOW workflow recommendations for IDH-mutant tumors and a framework for future resource and testing allocation.

A Unique Case Report of Infant-Type Hemispheric Glioma (Gliosarcoma Subtype) with TPR-NTRK1 Fusion Treated with Larotrectinib.

Herein, we present a rare case of a nine-month-old boy diagnosed with infant-type hemispheric glioma (gliosarcoma subtype) at the left frontal lobe. Following subtotal resection, the patient started chemotherapy with the BABY POG protocol. We describe the clinical diagnosis, histological characteristics, radiological features, molecular aspects, and management of this tumor. A comprehensive molecular analysis on the tumor tissue showed a TPR-NTRK1 gene fusion. The patient was treated with a TRK inhibitor, larotrectinib, and exhibited a stable disease with residual lesion following 8 months of target therapy. The present study is the first report of an infantile gliosarcoma harboring NTRK1 rearrangement treated with larotrectinib.

Microbiota Profile and Impact of Fusobacterium nucleatum in Colorectal Cancer Patients of Barretos Cancer Hospital.

Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of Fusobacterium nucleatum (Fn) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with Fusobacterium being the most abundant genus in the tumor tissue. In the validation dataset, Fn was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor (p = 0.0033). Fn DNA in the tumor tissue was significantly associated with proximal tumors (p = 0.001), higher depth of invasion (p = 0.014), higher clinical stages (p = 0.033), poor differentiation (p = 0.011), MSI-positive status (p < 0.0001), BRAF mutated tumors (p < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 (p < 0.0001), MSH2 (p = 0.003), and PMS2 (p < 0.0001). Moreover, the presence of Fn DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; p = 0.028) and overall survival (63.5 vs. 76.5%; p = 0.037). Here we report, for the first time, the association of F. nucleatum presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.

An unusual presentation of giant pilomatrixoma in an adult patient.

BACKGROUND: Pilomatrixoma (OMIM ID #132600) is a benign cutaneous tumor originating from the pilosebaceous follicle and characterized by the presence of subcutaneous nodules of up to 3.0 cm in diameter, usually on the head, neck and upper extremities. It is most common in the first two decades of life and after the age of 60. MAIN OBSERVATIONS: An adult female patient was evaluated, presenting a solid tumoral lesion with erythematous surface and purplish tone, with approximately 7.5 x 5.0 cm in size, in the interscapulovertebral region. It was thought to be an epidermoid cyst, sarcoma, calcified hemangioma, giant dermatofibroma, or nodular basal cell carcinoma. The resection of the lesion was carried out and, at the histological examination, specific details were observed that led to the diagnosis of pilomatrixoma. CONCLUSION: Pilomatrixoma should be suspected in the differential diagnosis of giant adnexal tumors.

Treatment of rectal leiomyoma by endoscopic resection

Leiomyomas of the rectum are rare, with low reported incidence in literature. In most cases, patients are asymptomatic, and are often incidental endoscopic findings. The difficult distinction from leiomyosarcomas, associated with the possibility of recurrence, implies the absence of a standard treatment. Endoscopic resection, if well indicated, may be a therapeutic option. In this study, we report two cases of asymptomatic leiomyoma of the rectum in two patients, discovered incidentally during a routine colonoscopy, removed by conventional polypectomy and discuss its diagnostic and therapeutic aspects based on a literature review. (AU)

Os leiomiomas de reto são raros, com baixa incidência relatada na literatura; na maioria dos casos os pacientes são assintomáticos, sendo que em muitos casos são achados incidentais endoscópicos. A dificuldade de distinguí-los dos leiomiossarcomas, aliada a possibilidade de recorrência, implica na inexistência de um tratamento padrão. A ressecção endoscópica desde que bem indicada pode ser uma opção terapêutica. Reportamos dois casos de leiomioma de reto assintomáticos em dois pacientes, descobertos casualmente durante exame colonoscópico de rotina, removidos por polipectomia convencional e discutimos seus aspectos diagnósticos e terapêuticos, através de uma revisão da literatura. (AU)

Diagnostic accuracy of frozen section tests for surgical diseases.

OBJECTIVE: To evaluate the accuracy of frozen section tests at different anatomical sites performed in an academic department of pathology. METHODS: We conducted a retrospective study from a computerized database of all frozen section tests. These diagnoses were compared to definite paraffin, used as controls. The tests were divided into three groups: inconclusive, consistent and inconsistent, the latter being subdivided into false positives and false negatives. The main indications for examinations and anatomical sites involved with diagnostic disagreements were also analyzed. RESULTS: Four hundred and thirty-three specimens were frozen tested, and the main indication was diagnostic (75.75%). In 404 tests (93.30%) diagnoses of biopsies in paraffin and frozen section were consistent. In 20 cases (4.62%) the results of frozen section biopsy were inconclusive and in 9 (2.08%) they were false negative. There were no false positive results. The most commonly assessed organ was the thyroid (25.64%). In the overall analysis, the body region most related with inconclusive diagnoses was the thyroid (seven cases) and in relation to specific sites it was the lungs/pleura/mediastinum (13.33%). Skin was the organ that showed more discordant diagnoses between frozen biopsies and paraffin. CONCLUSION: The global accuracy of frozen section was 93.30%; for specific anatomical sites, diagnostic accuracy ranged from 86.67% to 100%.

Precisão diagnóstica das doenças cirúrgicas nos exames por congelação / Diagnostic accuracy of frozen section tests for surgical diseases

OBJETIVO: Avaliar o grau de precisão diagnóstica dos exames por congelação em diferentes sítios anatômicos realizados em um serviço universitário de patologia. MÉTODOS: Foi realizado estudo retrospectivo a partir de banco de dados informatizado de todos os exames por congelação. Estes diagnósticos foram comparados com os definitivos em parafina, utilizados como controles. Os exames foram distribuídos em três grupos: inconclusivos, concordantes e não concordantes, sendo este último subdivido em falsos positivos e falsos negativos. As principais indicações dos exames e os sítios anatômicos envolvidos com as divergências diagnósticas também foram analisados. RESULTADOS: Quatrocentas e trinta e três peças cirúrgicas foram submetidas a exames por congelação, sendo a principal indicação o diagnóstico da lesão (75,75 por cento). Em 404 exames (93,30 por cento) os diagnósticos das biópsias por congelação e em parafina foram concordantes. Em 20 (4,62 por cento) casos os resultados das biópsias por congelação foram inconclusivos e em nove (2,08 por cento) ocorreram falsos negativos. Não houve resultados falsos positivos. O principal órgão avaliado foi a tireoide (25,64 por cento). Na análise global, a região do corpo mais relacionada com os diagnósticos inconclusivos por congelação foi a tireoide (sete casos) e em relação aos sítios específicos foram os pulmões/pleura/mediastino (13,33 por cento). Pele foi o órgão que mais apresentou diagnósticos discordantes entre biópsias por congelação e em parafina. CONCLUSÃO: A acurácia da congelação de forma global foi de 93,30 por cento; por sítios anatômicos específicos, a precisão diagnóstica variou de 86,67 por cento a 100 por cento.

OBJECTIVE: To evaluate the accuracy of frozen section tests at different anatomical sites performed in an academic department of pathology. METHODS: We conducted a retrospective study from a computerized database of all frozen section tests. These diagnoses were compared to definite paraffin, used as controls. The tests were divided into three groups: inconclusive, consistent and inconsistent, the latter being subdivided into false positives and false negatives. The main indications for examinations and anatomical sites involved with diagnostic disagreements were also analyzed. RESULTS: Four hundred and thirty-three specimens were frozen tested, and the main indication was diagnostic (75.75 percent). In 404 tests (93.30 percent) diagnoses of biopsies in paraffin and frozen section were consistent. In 20 cases (4.62 percent) the results of frozen section biopsy were inconclusive and in 9 (2.08 percent) they were false negative. There were no false positive results. The most commonly assessed organ was the thyroid (25.64 percent). In the overall analysis, the body region most related with inconclusive diagnoses was the thyroid (seven cases) and in relation to specific sites it was the lungs/pleura/mediastinum (13.33 percent). Skin was the organ that showed more discordant diagnoses between frozen biopsies and paraffin. CONCLUSION: The global accuracy of frozen section was 93.30 percent; for specific anatomical sites, diagnostic accuracy ranged from 86.67 percent to 100 percent.

Ectopic thyroid presenting as a submandibular mass.

Although extremely rare, the presence of ectopic thyroid tissue in the submandibular region should be considered in the differential diagnosis of tissue masses in the cervical region. Diagnosis is confirmed by fine-needle aspiration biopsy and exclusion of malignancy should be confirmed by histopathologic analysis of the lesion. In general, surgery is the treatment of choice. A rare case of ectopic thyroid in the right submandibular region is reported; it was diagnosed after total thyroidectomy and successfully treated through surgery.

Distribuição de proteoglicanos nas vias aéreas na asma fatal / Airway proteoglycan distribution in fatal asthma

Tem sido sugerido que o remodelamento brônquico é o responsvel pela obstrução persistente das vias aéreas e pelo declínio na função pulmonar observados em alguns pacientes asmáticos. Os proteoglicanos (PGs) são componentes importantes da matriz extracelular (MEC) dos pulmões. Além de controlar propriedades biofísicas da Mec, têm importantes ações regulatórias em algumas citocinas./ It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patientes. Proteoglycans (PGs) ar important components of the extracellular matrix (ECM) in the lungs...

Prostate carcinoma with neuroendocrine differentiation: case report and literature review

Neuroendocrine differentiation in prostatic carcinomas generally confers a more aggressive clinical behavior and less favorable prognosis than usual prostatic carcinomas. In this manuscript, we report a case of a 58-year-old man with prostatic carcinoma who died 1 year after initial diagnosis. Autopsy showed a disseminated prostatic carcinoma with neuroendocrine differentiation. There were metastasis to the spleen, an organ infrequently involved by disseminated epithelial neoplasms. Neuroendocrine differentiation was demonstrated by immunohistochemical studies in the biopsy and autopsy material