Search

Purpose Osteomyelitis of the sternum may arise either as a primary condition or secondary to median thoracotomy after cardiac surgery, with the latter being decidedly more frequent. Deep sternal wound infections appear as a complication of median thoracotomy in 0.2 to 4.4% of cases and may encompass the infection of the sternal bone. To date, there are no exhaustive histopathological studies of the sternal osteomyelitis. Methods Our work group developed a surgical technique to remove the complete infected sternal bone in deep sternal wound infections. We therefore prospectively examined the en bloc resected sternal specimens. Seven standard histological sections were made from the two hemisternums. Results Forty-seven sternums could be investigated. The median age of the patients in the cohort was 66 (45–81) years and there were 10 females and 37 males. Two methods were developed to examine the histological findings, with one model dividing the results in inflammatory and non-inflammatory, while the second method using a score from 0 to 5 to describe more precisely the intensity of the bone inflammation. The results showed the presence of inflammation in 76.6 to 93.6% of the specimens, depending on the section. The left manubrial sections were more prone to inflammation, especially when the left mammary artery was harvested. No further risk factors proved to have a statistical significance. Conclusion Our study proved that the deep sternal wound infection may cause a ubiquitous inflammation of the sternal bone. The harvest of the left mammary artery may worsen the extent and intensity of infection.

The last 2 decades have attended a dynamic evolution in the nosology of poorly differentiated sinonasal tract malignancies, with several new molecularly defined entities having been described in addition to delineation of the genetic driver/s of some established older entities. These discoveries, however, mostly concerned epithelial-derived neoplasms (carcinomas). Adamantinoma-like Ewing sarcoma and biphenotypic sinonasal sarcoma are the major representatives of the newly defined mesenchymal categories. The colorectal cancer associated 2 (COLCA2) has been discovered recently as a colorectal cancer risk gene locus, but fusions involving this gene have not been well characterized. We, herein, describe clinicopathologic and molecular features of a novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and defined by recurrent EWSR1::COLCA2 fusions. All patients (n=5) were adults (3 female and 2 male) with a median age of 46 years (range, 23 to 60 y). The tumors originated in different subsites of the sinonasal tract with frequent multisite involvement. Original diagnoses were undifferentiated or unclassified round cell/spindle cell neoplasm/sarcoma (n=4) and neuroendocrine carcinoma (n=1). Surgery with or without adjuvant chemoradiation was the treatment in all cases. At the last follow-up, 1 patient developed multiple local recurrences over 21 years and another developed local recurrence and distant metastasis to bone 27 months after diagnosis. A third patient developed local recurrence 11 months later. Two patients were disease-free at 23, and 24 months. Histology showed nondescript highly cellular neoplasms with an admixture of spindled and round cells disposed into solid sheets and fascicles with brisk mitotic activity. Immunohistochemistry was negative for all lineage-specific markers with only limited focal membranous CD99 (4 of 5 cases) and weak pankeratin (1 of 5 cases) expression. Targeted RNA sequencing revealed an EWSR1::COLCA2 fusion, verified by EWSR1 fluorescence in situ hybridization, in all cases. This series identifies a novel member in the undifferentiated spindle/round cell sarcoma category with strong predilection for the sinonasal tract. None of10,000 epithelial and mesenchymal neoplasms tested at the authors' centers during the same period showed this fusion, highlighting rarity of tumors carrying this gene fusion. Accordingly, molecular testing of unclassified sinonasal malignancies/sarcomas showing round and spindle cell morphology is recommended to enhance the identification and further characterization of this entity.

Purpose Osteomyelitis of the sternum may arise either as a primary condition or secondary to median thoracotomy after cardiac surgery, with the latter being decidedly more frequent. Deep sternal wound infections appear as a complication of median thoracotomy in 0.2 to 4.4% of cases and may encompass the infection of the sternal bone. To date there are no exhaustive histopathological studies of the sternal osteomyelitis. Methods Our work group developed a surgical technique to remove the complete infected sternal bone in deep sternal wound infections. We therefore prospectively examined the en bloc resected sternal specimens. Seven standard histological sections were made from the two hemisternums. Results Forty-seven sternums could be investigated. The average age of the patients in the cohort was 67 (45–81) years and there were 10 females and 37 males. Two methods were developed to examine the histological findings, with one model examining dividing the results in inflammatory and non-inflammatory, while the second method using a score from 0 to 5 to describe more precisely the intensity of the bone inflammation. The results showed the presence of inflammation in 76.6–93.6% of the specimens, depending on the section. The left manubrial sections were more prone to inflammation, especially when the left mammary artery was harvested (LIMA). No further risk factors proved to have a statistical significance. Conclusion Our study proved that the deep sternal wound infection may cause a ubiquitous inflammation of the sternal bone, which justifies the complete sternectomy. The harvest of the left mammary artery may worsen the extent and intensity of infection.

Background: Data on institutional structures of sarcoma care in Germany are scarce. The utilization of an interdisciplinary tumor board (IDTB) is an essential part of modern cancer care. We investigated to which extent and when IDTB are used in sarcoma care. We hypothesized that IDTB before treatment initiation were used more often at certified cancer centers and at high-volume centers and that IDTB utilization increased over time. Methods: From 2017 to 2020 we conducted a prospective cohort study, undertaking major efforts to include the whole spectrum of sarcoma treatment facilities. To analyze potential predictors of IDTB utilization, we calculated multivariable logistic regressions. Results: Patients and survivors (n = 1,309) from 39 study centers (22 tertiary referral hospitals, 9 other hospitals, and 8 office-based practices) participated; 88.3% of the patients were discussed at some stage of their disease in an IDTB (56.1% before treatment, 78% after therapy, and 85.9% in metastatic disease). Hypotheses were confirmed regarding the utilization of IDTB in certified cancer centers (vs. all others: OR = 5.39; 95% CI 3.28–8.85) and the time of diagnosis (2018/2019 vs. until 2013: OR = 4.95; 95% CI 2.67–9.21). Conclusion:Our study adds to the evidence regarding the institutional structures of sarcoma care in Germany. Utilization of a tumor board before therapy seems to be in an implementation process that is making progress but is far from complete. Certification is a possible tool to accelerate this development.

Virchows Archiv (2022). doi:10.1007/s00428-022-03319-2, Published by Springer, Berlin

The lancet / Regional health. Europe 15, 100330 (2022). doi:10.1016/j.lanepe.2022.100330, Published by Elsevier, [Amsterdam]

Modern pathology 35(8), 1013-1021 (2022). doi:10.1038/s41379-022-01069-9, Published by Nature Publishing Group, London

Virchows Archiv 480(3), 519-528 (2022). doi:10.1007/s00428-021-03263-7, Published by Springer, Berlin ; Heidelberg

Here we report a possible mechanistic link between coronavirus disease 2019 (COVID-19) and diabetes. In addition to its known role on the respiratory system, the human coronavirus SARS-CoV-2 has been shown to affect the endocrine system including the pancreas 1-4. It has been suggested that the virus can induce type 1 diabetes 5-8. Therefore, we isolated human pancreatic islets and examined the expression of angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2, known to be important for SARS-CoV-2 entry 9. Furthermore, we investigated the expression of an alternative entry receptor, dipeptidyl peptidase-4 (DPP4 also known as CD26) 10. We found all three proteins expressed in pancreatic beta-cells and confirmed that beta-cells are permissive to infection with SARS-CoV-2 pseudoviruses. Additionally, we performed a comprehensive analysis of ACE2, TMPRSS2 and DPP4 expression in pancreata of 10 patients who died of COVID-19. We report significant variation between the samples and detected the highest levels of ACE2 and DPP4 expression in patients exhibiting SARS-CoV-2 infiltration shown by confocal microscopy, RNAscope and electron microscopy. Furthermore, necroptotic cell death was observed in beta-cells of the COVID-19 patients. Taken together, these data suggest that SARS-CoV-2 viral infection of pancreatic beta-cells may trigger necroptosis and islet impairment.

IgG4-related disease (IgG4-RD) is an inflammatory disorder characterized by tumor-like swelling in one or more organs, elevated serum IgG4 levels, and histological alterations with infiltration of IgG4-positive plasma cells. IgG4-RD is rare and likely underdiagnosed in children. We report a case of a 16-year-old girl with IgG4-positive colitis that developed weeks after IgG4-related ophthalmic disease and discuss diagnosis and treatment in the context of the literature available. Since the pathophysiology of IgG4-RD is unknown, treatment options are empiric and, for the most part, untargeted. Systemic corticosteroid treatment is the basis of anti-inflammatory treatment in IgG4-RD and induced early remission in our patient. During corticosteroid taper, the patient developed weight loss and intestinal inflammation. Histopathological assessment of the intestinal walls confirmed IgG4-positive colitis. Immune-modulating treatment with non-biologic (e.g., methotrexate (MTX) and mycophenolate mofetil) or biologic (rituximab) disease-modifying antirheumatic drugs has been reported in treatment refractory or corticosteroid-dependent patients. The patient responded to treatment with anti-inflammatory therapy with food rich in TGF-β2 (modulen) and MTX. This is one of the first pediatric patients reported with IgG4-related colitis extending the phenotype of pediatric IgG4-RD. International collaboration to prospectively document clinical presentation and treatment responses may help to further establish the phenotype and treatment options and to raise awareness for IgG4-RD.

Purpose of Review Chronic non-bacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder. We summarize the clinical presentation, diagnostic approaches, most recent advances in understanding the pathophysiology, and available treatment options and outcomes in CNO/CRMO. Recent Findings Though the exact molecular pathophysiology of CNO/CRMO remains somewhat elusive, it appears likely that variable defects in the TLR4/MAPK/inflammasome signaling cascade result in an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes from CNO/CRMO patients. In this context, we present previously unpublished data on cytokine and chemokine expression in monocytes and tissues. Summary CNO/CRMO is an autoinflammatory bone disorder resulting from imbalanced cytokine expression from innate immune cells. Though the exact molecular pathophysiology remains unclear, variable molecular defects appear to result in inflammasome activation and pro-inflammatory cytokine expression in monocytes from CNO/CRMO patients. Recent advances suggest signaling pathways and single molecules as biomarkers for CNO/CRMO as well as future treatment targets.

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

Background Ganglioneuromatous polyposis (GP) is a very rare disorder which may be associated with other clinical manifestations and syndromes, such as Cowden syndrome, multiple endocrine neoplasia (MEN) type II and neurofibromatosis (NF) 1. The risk for malignant transformation of ganglioneuromas is unknown, and the combination of GP with colon cancer has been only very seldom reported. Methods and results We report the case of a 60-year old male patient with adenocarcinoma, adenomas and lipomas of the colon and multiple gastroduodenal lesions combined with generalised lipomatosis and macrocephaly. Based on the initial endoscopic and histological findings, a (restorative) proctocolectomy was recommended but declined by the patient. Instead, a colectomy was performed. The histological examination revealed an unforeseen GP in addition to the colon cancer. Extensive molecular diagnostics allowed for the differential diagnosis of the causes of the clinical manifestations, and the clinical suspicion of Cowden syndrome could not be confirmed using Sanger Sequencing and MLPA for the analysis of PTEN. Finally, a pathogenic germline mutation in PTEN (heterozygous stop mutation in exon 2: NM_000314 (PTEN):c.138C > A; p.Tyr46*) could be detected by next-generation sequencing (NGS), confirming an unusual presentation of Cowden syndrome with GP. Conclusions Cowden syndrome should be considered in cases of GP with extracolonic manifestation and verified by combined clinical and molecular diagnostics. Because GP may represent a premalignant condition, a surgical-oncological prophylactic procedure should be considered. Based on our experience, we recommend early implementation of Panel NGS rather than classical Sanger sequencing for genetic diagnostics, especially if various diagnoses are considered.

Background Hibernomas are rare benign soft-tissue tumours arising from brown fat tissue. Although imaging characteristics are not specific certain imaging features, common locations and patient demographics may suggest hibernoma as a differential diagnosis. Case presentation We report on two 48-year-old male patients with hibernoma. The tumour presented with local swelling of the inguinal region in the first patient and was an incidental imaging finding in the second patient. Imaging included magnetic resonance imaging in both patients and computed tomography as well as 18 F-fluorodeoxyglucose positron emission tomography-computed tomography in the second patient. In both cases histological diagnosis was initially based on excisional and needle core biopsy, respectively. Complete surgical resection confirmed the diagnosis of hibernoma thereafter. Conclusion In soft tissue tumours with fatty components hibernoma may be included into the differential diagnosis. Because of the risk of sampling errors in hibernoma-like tissue components of myxoid and well-differentiated liposarcoma, complete resection is mandatory. This article also reviews the current imaging literature of hibernomas.

Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated.