Application of a pattern-based approach to histological diagnosis in very early onset IBD (VEO-IBD) in a multicentric cohort of children with emphasis on monogenic disease with IBD-like morphology.

AIMS: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy. METHODS AND RESULTS: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies. CONCLUSIONS: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion.

Synchronous Endometrial and Ovarian Carcinomas: Pathologic and Molecular Analysis Highlights the Monoclonal Origin of the Lesions.

The diagnosis of synchronous carcinomas, involving both the endometrium and ovaries, is not a rare finding in gynecologic pathology and represents a challenge with implications on tumor staging and therapeutic decision-making. A mono-institutional series of 11 metastatic and 6 paired synchronous endometrial and ovarian carcinomas were reviewed by 2 expert pathologists based on previously published histopathologic criteria. The series was investigated for DNA mismatch repair proteins, p53, and POLE status and was subject to DNA-based next-generation sequencing targeting 67 cancer-related genes. Out of 17 pairs, 16 featured the same histotype (10 endometrioid, 4 serous high-grade, and 2 clear cells). By using WHO 2020 criteria, 11 couples of tumors were confirmed as metastatic and 6 couples were confirmed as independent. Based on next-generation sequencing analysis, 16 of 17 cases (11 metastatic and 5 independent) of our series showed evidence of a clonal relationship between endometrial and ovarian carcinomas. In metastatic cases, the adverse outcome was associated with nonendometrioid/high-grade endometrioid histotype and with the p53-abnormal molecular subtype. Four cases originally fulfilling clinicopathological criteria of independent endometrial and ovarian carcinomas were clonally related, low-grade endometrioid histotype and POLE-mut, mismatch repair deficient, and no specific molecular profile molecular subtypes; no adverse event was recorded in this group. In summary, the molecular characterization of synchronous gynecologic carcinomas confirms their clonal origin in most cases. However, the results of our study point out that the clinical behavior of these tumors seems to be determined by the presence of high-risk WHO 2020 histologic criteria and molecular features (i.e. p53-abnormal), rather than the monoclonal origin.

Enhancing diagnosis of Hirschsprung's disease using deep learning from histological sections of post pull-through specimens: preliminary results.

PURPOSE: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology. METHODS: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves. RESULTS: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%. CONCLUSION: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists.

A rare case of extrarenal Wilms tumor of the uterine corpus: comprehensive genomic profile and review of the literature.

Wilms tumor (WT), or nephroblastoma, is an uncommon malignant neoplasm occurring in the kidney of pediatric patients. Its extrarenal location is extremely rare and has been reported in various sites, including the female genital tract, with only 9 cases arising in the uterine corpus. We present the case of an adult woman who underwent total abdominal hysterectomy due to a uterine mass causing persistent abdominal pain. The characteristic triphasic morphology (composed of epithelial, stromal, and blastemal elements) supported by a broad immunohistochemical panel, along with the imaging exclusion of a renal neoplasm, was diagnostic of WT of the uterus. For the first time, a comprehensive genomic profiling of a uterine primary WT was also performed by next-generation sequencing, disclosing alterations at the level of copy number variations in the genes ERBB2, FGFR23, FGF6, FGFR2, and RPS6KB1. All previously reported uterine cases were reviewed, with a summary of their main clinicopathologic characteristics, and the main differential diagnoses are presented. Further reports are needed to improve our knowledge about prognostic factors, clinical behavior and molecular alterations that could guide appropriate therapeutic decision making.

Congenital anomalies of the gastrointestinal tract: the liver, extrahepatic biliary tree and pancreas.

Congenital anomalies of the liver, biliary tree and pancreas are rare birth defects, some of which are characterized by a marked variation in geographical incidence. Morphogenesis of the hepatobiliary and pancreatic structures initiates from two tubular endodermal evaginations of the most distal portion of the foregut. The pancreas develops from a larger dorsal and a smaller ventral outpouching; emergence of the two buds will eventually lead to the fusion of the duct system. A small part of the remaining ventral diverticulum divides into a "pars cystica" and "pars hepatica", giving rise to the cystic duct and gallbladder and the liver lobes, respectively. Disruption or malfunctioning of the complex mechanisms leading to the development of liver, gallbladder, biliary tree and pancreas can result in numerous, albeit fortunately relatively rare, congenital anomalies in these organs. The type and severity of anomalies often depend on the exact moment in which disruption or alteration of the embryological mechanisms takes place. Many theories have been brought forward to explain their embryological basis; however, no agreement has yet been reached for most of them. While in some cases pathological evaluation might be more centered on macroscopic evaluation, in other instances small biopsies will be the keystone to understanding organ function and treatment results in the context of congenital anomalies. Thus, knowledge of the existence and histopathological characteristics of some of the more common conditions is mandatory for every pathologist working in the field of gastrointestinal pathology.

New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups.

Pediatric solid neoplasms are rare and very different from those observed in adults. The majority of them are referred to as embryonal because they arise as a result of alterations in the processes of organogenesis or normal growth and are characterized by proliferation of primitive cells, reproducing the corresponding tissue at various stages of embryonic development. This review will focus on embryonal gastrointestinal pediatric neoplasms in adult patients, including pancreatoblastoma, hepatoblastoma, and embryonal sarcoma of the liver. Although they are classically considered pediatric neoplasms, they may (rarely) occur in adult patients. Hepatoblastoma represents the most frequent liver neoplasm in the pediatric population, followed by hepatocellular carcinoma and embryonal sarcoma of the liver; while pancreatoblastoma is the most common malignant pancreatic tumor in childhood. Both in children and adults, the mainstay of treatment is complete surgical resection, either up front or following neoadjuvant chemotherapy. Unresectable and/or metastatic neoplasms may be amenable to complete delayed surgery after neoadjuvant chemotherapy. However, these neoplasms display a more aggressive behavior and overall poorer prognosis in adults than in children, probably because they are diagnosed in later stages of diseases.

On the mechanism of tumor cell entry of aloe-emodin, a natural compound endowed with anticancer activity.

Aloe-emodin (1,8-dihydroxy-3-[hydroxymethyl]-anthraquinone), AE, is one of the active constituents of a number of plant species used in traditional medicine. We have previously identified, for the first time, AE as a new antitumor agent and shown that its selective in vitro and in vivo killing of neuroblastoma cells was promoted by a cell-specific drug uptake process. However, the molecular mechanism underlying the cell entry of AE has remained elusive as yet. In this report, we show that AE enters tumor cells via two of the five somatostatin receptors: SSTR2 and SSTR5. This observation was suggested by gene silencing, receptor competition, imaging and molecular modeling experiments. Furthermore, SSTR2 was expressed in all surgical neuroblastoma specimens we analyzed by immunohistochemistry. The above findings have strong implications for the clinical adoption of this natural anthraquinone molecule as an antitumor agent.

Pediatric Benign Tumors With a Skeletal Muscle Component: Myogenin Expression, Diagnostic Pitfalls, and New Molecular Insights.

OBJECTIVES: Benign tumors with skeletal muscle differentiation are rare and their characterization in the literature is limited. We present a series of twelve pediatric benign tumors with rhabdomyomatous differentiation including seven rhabdomyomatous mesenchymal hamartomas, four fetal rhabdomyomas, and one benign triton tumor, analyzing myogenic markers as well as clinicopathologic and molecular features. A review of the literature was also performed with an emphasis on myogenic marker expression and correlation with molecular features. METHODS AND RESULTS: Cases obtained from three tertiary pediatric hospitals were retrospectively reviewed. Eleven of twelve cases expressed myogenin in rare to greater than 15% of cells. Five of nine cases had rare to 70-80% of cells positive for MyoD1. One fetal rhabdomyoma demonstrated homozygous deletions in ZEB2. The benign triton tumor harbored a CTNNB1 mutation. Review of the literature identified 160 pediatric benign tumors with skeletal muscle differentiation of which 9 reported myogenin positivity. CONCLUSIONS: Myogenin and MyoD1 may be variably expressed in benign lesions with skeletal muscle differentiation. Recognition of key morphologic features remains critical to diagnose these lesions and, in rhabdomyoma, to exclude malignancy. Our series expands the knowledge of the relationship between rhabdomyoma and rhabdomyosarcoma (RMS) by identifying a shared molecular alteration in ZEB2.

Infantile inflammatory myofibroblastic tumors: clinicopathological and molecular characterization of 12 cases.

Inflammatory myofibroblastic tumors arising in infants are rare, poorly investigated and mostly reported as isolated cases or as a part of larger series thus, their clinicopathological and molecular features are essentially unknown. Archival files from two large pediatric institutions and a tumor registry were queried for pediatric inflammatory myofibroblastic tumors. Available material from patients ≤12 months of age was reviewed. Additional immunostains (ALK-1, D240, WT1) and ALK-FISH studies were performed as needed. Targeted anchored multiplex PCR with next-generation sequencing was done in all cases. A total of 12 of 131 infantile cases (mean 5.5 months) were identified (M:F of 2:1). Anatomic locations included intestinal/mesenteric (n = 6), head/neck (n = 3), and viscera (n = 3). Half of tumors showed a hypocellular myxoid pattern, perivascular condensation, and prominent vasculature with vague glomeruloid structures present in four of them. The remaining cases exhibited a more cellular pattern with minimal myxoid component. ALK-1 immunohistochemistry was positive in most cases (11/12) with cytoplasmic-diffuse (n = 6), cytoplasmic-granular (n = 2), and dot-like (n = 3) staining patterns. ALK fusion partners identified in five cases included EML4, TPM4, RANBP2, and a novel KLC1. Three inflammatory myofibroblastic tumors showed fusions with other kinases including TFG-ROS1 and novel FN1-ROS1 and RBPMS-NTRK3 rearrangements. Favorable outcome was documented in most cases (10/11) with available follow-up (median 17 months) while three patients were successfully treated with crizotinib. In summary, infantile inflammatory myofibroblastic tumors are rare and can exhibit paucicellular, extensively myxoid/vascular morphology with peculiar immunophenotype mimicking other mesenchymal or vascular lesions. All tumors harbored kinase fusions involving ALK, ROS1, and NTRK3 including three novel fusion partners (KLC1, FN1, and RBPMS, respectively). A favorable response to crizotinib seen in three cases supports its potential use in infants as seen in older patients. Awareness of these unusual morphologic, immunophenotypic, and molecular features is critical for appropriate diagnosis and optimized targeted therapy.

Dermatofibrosarcoma protuberans in children and adolescents: The European Paediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005).

BACKGROUND: As dermatofibrosarcoma protuberans (DFSP) are rare with no prospective series within paediatric sarcoma trials, the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) examined the clinical data and outcomes of DFSP enrolled in a multinational study of non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). PATIENTS AND METHODS: Forty-six patients with confirmed DFSP were enrolled into the EpSSG NRSTS 2005 study. All had surgical resection and none had any further therapy at diagnosis. RESULTS: The median age at diagnosis was 6.9 years (range 0.4-17.5). All patients had localised disease, and the majority had small <5 cm tumours (93%), and 76% had Intergroup Rhabdomyosarcoma Study (IRS) I tumours. All patients had up front surgery, 32 requiring two operations. There were 11 patients with IRS II tumours, of which only two went on to have a local recurrence. After a median follow up of 49.0 months (range 4.2-130.9), all patients were alive at the time of this report, with 5-year event-free survival of 92.6% (CI 78.8-97.6) with a 100% overall survival. CONCLUSION: This report demonstrates the ability to run prospective paediatric studies in NRSTS in multiple European countries, with reasonable numbers of DFSP patients, with few events and no deaths, and hence excellent outcomes.

Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease.

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas' heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

Anti-Glypican 3, a Novel Ancillary Maker in the Histological Assessment of Hirschsprung's Disease.

OBJECTIVES: Hirschsprung's disease (HSCR) results from a malformation of the enteric nervous system. A congenital absence of intrinsic ganglion cells from the distal rectum and a variable length of the contiguous bowel is the required diagnostic feature of Hirschsprung's disease and total colonic aganglionosis (TCA). We evaluated the utility of a monoclonal antibody directed against glypican 3 (GPC-3), a membrane bound protein involved in regulation of the signaling of Wingless-types (WNTs), Hedgehogs (Hh), Fibroblast Growth Factors (FGFs), and Bone Morphogenetic Proteins (BMPs), in the detection of ganglion cells in formalin-fixed, paraffin-embedded tissue sections. METHODS: The presence/absence of ganglion cells was evaluated retrospectively by immunohistochemical staining for calretinin and GPC-3 in tissue specimens; a total of 15 patients who underwent colectomy (total or sub-total) for histologically proven aganglionosis (14 HSCR, 1 TCA) and 5 rectal suction biopsies (4HSCR-B, 1 TCA-B) were considered. Of the 20 considered cases, a total of 60 tissue specimens (3 for each patient) were selected. A total of 30 additional normal (N) colonic mucosa biopsy samples were also included. RESULTS: GPC-3 constantly identified ganglion cell bodies in all but 2 normal biopsies (with normal presentation of ganglion cells on hematoxylin and eosin (H&E) stain), and was negative in all 60 aganglionotic biopsies; these results were reflective of calretinin staining pattern. CONCLUSIONS: The present study indicates that monoclonal anti-GPC-3 might prove to be useful immunohistochemical marker in the identification of ganglion cells in paraffin-embedded rectal tissue specimens and suction biopsies. Further studies in larger series will contribute to demonstrate its utility as an ancillary marker in the histological assessment of HSCR aganglionosis.

Large B-cell lymphoma with IRF4 rearrangement: a multi-centric study with focus on potential misleading phenotypes.

Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) is a rare lymphoid neoplasm, usually occurring in the pediatric/young-adult age. Despite this, subsets of cases occur in elderly patients and express CD5, possibly entering the differential diagnosis with adult aggressive lymphomas, such as blastoid/pleomorphic mantle cell lymphoma (MCL-B/P). To better characterize the clinical-pathological features and differential diagnosis of LBCL-IRF4, we conducted a multi-centric study on 12 cases, focusing on CD5, Cyclin D1, and SOX11 expression. While most cases had typical presentation, adult-to-elderly age at diagnosis and unusual anatomic locations were reported in 3/12 (25.0%) and 2/12 (16.7%) patients, respectively. Histologically, CD5 was positive in 4/12 (33.3%) cases, Cyclin D1 was invariably negative, and SOX11 was weakly/partially expressed in 1/12 (8.3%) case. In conclusion, LBCL-IRF4 can have unconventional clinical presentations that may challenge its recognition. Although CD5 is frequently expressed, negativity for Cyclin D1 and SOX11 contributes to the differential diagnosis with MCL-B/P.

Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms.

Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]). In adults, the reticulin algorithm (RA) has proven inexpensive, reliable, predictive, and reproducible; however, it has been validated only recently in children in a limited number of cases. This study aims to assess the RA utility compared with other scoring systems in a series of 92 pediatric ACNs. All cases were individually scored, and mitotic rate cutoffs were recorded. Reticulin alterations were classified as quantitative and qualitative. Outcome data were available in 59/92. The median age was 5 years (0.1 to 18 y) with an M:F of 0.6. Clinical presentation included virilization (39%), Cushing syndrome (21%), other symptoms (4%), and asymptomatic (36%). The reticulin framework was intact in 27% and altered in 73% of cases, showing qualitative (22%), quantitative (73%), and both (5%) alterations. In patients with favorable outcomes, 59% showed either intact reticulin or qualitative alteration compared with the unfavorable outcome group, where 90% showed quantitative alterations. All scoring systems WC ( P < 0.0001), mWC ( P = 0.0003), and the adult/pediatric RA ( P < 0.0001) had predictive value. The RA is comparable to WC and mWC, easier to apply, and is the most sensitive histopathological approach to identifying aggressive behavior in pediatric ACN. Its integration into the WC might be helpful in ACN of uncertain malignant potential and deserves further investigation.

Fetal Lung Interstitial Tumor (FLIT): Review of The Literature.

Fetal lung interstitial tumor (FLIT) is an extremely rare pediatric lung tumor that shares radiological features with congenital pulmonary malformations (cPAM) and other lung neoplasms. A review of the literature, together with the first European case, are herein reported. A systematic and manual search of the literature using the keyword "fetal lung interstitial tumor" was conducted on PUBMED, Scopus, and SCIE (Web of Science). Following the PRISMA guidelines, 12 articles were retrieved which describe a total of 21 cases of FLIT, and a new European case is presented. A prenatal diagnosis was reported in only 3 out of 22 (13%) cases. The mean age at surgery was 31 days of life (1-150); a lobectomy was performed in most of the cases. No complications or recurrence of disease were reported at a mean follow-up of 49 months. FLIT is rarely diagnosed during pregnancy, may present at birth with different levels of respiratory distress, and requires prompt surgical resection. Histology and immunohistochemistry allow for the differentiation of FLIT from cPAM and other lung tumors with poor prognosis, such as pleuropulmonary blastoma, congenital peri-bronchial myofibroblastic tumor, inflammatory myofibroblastic tumor, and congenital or infantile fibrosarcoma.

Postoperative Hirschsprung's associated enterocolitis (HAEC): transition zone as putative histopathological predictive factor.

AIMS: Hirschsprung's-associated enterocolitis (HAEC) is the most severe complication of Hirschsprung disease (HD), and its pathogenesis is still unknown. Length of transition zone (TZ) interposed between aganglionic and normal bowel has been poorly explored as predictor for postoperative HAEC (post-HAEC). This study aimed to identify potential predictive factors for post-HAEC, with a particular focus on histopathological findings. METHODS: Data from Hirschsprung patients treated in a single Italian centre between 2010 and 2022 with a follow-up >6 months were collected. Thorough histopathological examination of the resected bowel was conducted, focusing on length of TZ and aganglionic bowel.The degree of inflammatory changes in ganglionic resected bowel was further obtained. Ultra-long HD, total colonic aganglionosis and ultra-short HD were excluded. Bivariate and multivariate regression analysis were performed. RESULTS: Thirty-one patients were included; 5 experienced preoperative HAEC (pre-HAEC) and later post-HAEC (16.1%), further 10 patients developed post-HAEC (total post-HAEC 48.38%). Pre-HAEC-history and a TZ<2.25 cm correlated with an early development of post-HAEC. Multivariate analysis identified a TZ<2.25 cm as an independent post-HAEC predictive factor (p=0.0096). Inflammation within the ganglionic zone and a TZ<2.25 cm correlated with higher risk of post-HAEC (p=0.0074, 0.001, respectively). Severe post-HAEC more frequently occurred in patients with pre-HAEC (p=0.011), histological inflammation (p=0.0009) and short TZ (p=0.0015). CONCLUSIONS: This study suggests that TZ<2.25 cm predicts the risk of post-HAEC. Preoperative clinical and histopathology inflammation may predispose to worst post-HAEC. Readily available histopathological findings might help identifying patients at higher risk for HAEC and implementing prevention strategies.

Higher accuracy of surgical over core needle biopsy for the diagnosis of lymphoproliferative disorders.

INTRODUCTION: The diagnosis of lymphoproliferative disorders (LPDs) is based on histological evaluation of representative tissue samples. Despite surgical excision biopsies (SEBs) are reference procedures for such diagnoses, lymph node core needle biopsies (LNCBs) are increasingly performed. The diagnostic yield of LNCB is, however, debated and few studies have compared the reproducibility of LNCB and SEB findings. METHODS: To address the diagnostic value of LNCB and SEB, the present study considered a retrospective series of 43 paired LNCB/SEB samples. After histological revision, concordance rates between matched LNCB/SEB samples were evaluated, assuming SEB as gold standard procedure. The actionability of LNCB and SEB-based diagnoses (i.e., relevance for planning further medical interventions) was also assessed. RESULTS: Overall, LNCB provided actionable diagnoses in 39/43 (90.7%) cases, but a consistent subset of them (7/39 [17.9%]) turned out to be wrong at SEB. The cumulative diagnostic inaccuracy of LNCB (i.e., inadequate samples plus wrong diagnoses) was 25.6% and the mean diagnostic delay in such cases was 54.2 days. CONCLUSIONS: Although limited by selection biases due to its retrospective nature, this study highlights the intrinsic limitations of LNCB for the diagnosis of LPDs. SEB remains the gold standard procedure and should be performed in all suitable cases.

Non-traumatic Myositis Ossificans as Unusual Cause of Neck Pain During COVID-19 Pandemic: a Case Report.

Myositis ossificans circumscripta (MOC) is a benign disease characterized by localized heterotopic bone formation within muscles or soft tissue, usually interesting great muscles of extremities. We report a rare case of unusual location in the neck not associated with previous trauma, mimicking a solid tumor, with well-documented diagnostic imaging features. During COVID-19 pandemic outbreak in Italy, in May 2020, a 14-year-old boy developed a progressive and persistent neck pain on the right side, without known history of trauma. Initial therapy with non-steroid anti-inflammatory drugs and physiokinetic therapy gave only a slight improvement. A neck ultrasound showed an inhomogeneous right neck mass, with posterior shadowing due to calcifications. Computed tomography and magnetic resonance imaging confirmed a huge right neck mass, located in the paravertebral space with peripheral calcifications and mild central contrast enhancement. After surgical excision of the lesion, pathology revealed the presence of muscular tissue mixed with fibroblastic/myofibroblastic proliferation and ossification areas consistent with myositis ossificans. A careful analysis of clinical and radiological features is very important to manage young patients showing progressive pain and swelling of the neck, since MOC can mimic soft tissue or bone tumors, and it should be suspected even in the absence of a known history of trauma.