Calcified Chondroid Mesenchymal Neoplasms.

Calcified chondroid mesenchymal neoplasms (CCMN) represent a morphologic spectrum of related tumors. Historically, chondroid matrix or chondroblastoma-like features have been described in soft tissue chondroma, tenosynovial giant cell tumors (especially of the temporomandibular joint (TMJ) region), and in a subset of tophaceous pseudogout. Recently, these tumors have been found to share FN1-receptor tyrosine kinase (RTK) fusions. This review discusses the clinical, morphologic, immunohistochemical, and molecular genetic features of CCMN. The distinction from morphologic mimics is also discussed.

Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor-A Clinicopathologic and Molecular Genetic Study of 11 Cases.

Malignant gastrointestinal neuroectodermal tumors (MGNETs), also known as "gastrointestinal clear cell sarcoma-like tumors", are very rare, aggressive sarcomas characterized by enteric location, distinctive pathologic features, and EWSR1/FUS::ATF1/CREB1 fusions. Despite identical genetics, the clinicopathologic features of MGNET are otherwise quite different from those of clear cell sarcoma of soft parts. Only exceptional extraenteric MGNET (E-MGNET) has been reported. We report a series of 11 E-MGNETs, the largest to date. Cases diagnosed with MGNET and occurring in nonintestinal locations were retrieved. A clinical follow-up was obtained. The tumors occurred in 3 men and 8 women (range, 14-70 years of age; median, 33 years) and involved the soft tissues of the neck (3), shoulder (1), buttock (2), orbit (1), tongue/parapharyngeal space (1), urinary bladder (1), and falciform ligament/liver (1). Tumors showed morphologic features of enteric MGNET (small, relatively uniform, round to ovoid cells with round, regular nuclei containing small nucleoli growing in multinodular and vaguely lobular patterns, with solid, pseudoalveolar, and pseudopapillary architecture). Immunohistochemical results were S100 protein (11/11), SOX10 (11/11), synaptophysin (3/10), CD56 (7/9), CD117 (3/9), DOG1 (0/4), ALK (4/8), chromogranin A (0/10), HMB-45 (0/11), Melan-A (0/11), tyrosinase (0/4), and MiTF (0/11). Next-generation sequencing results were EWSR1::ATF1 (7 cases), EWSR1::CREB1 (3 cases), and EWSR1::PBX1 (1 case). The EWSR1::PBX1-positive tumor was similar to other cases, including osteoclast-like giant cells, and negative for myoepithelial markers. A clinical follow-up (range, 10-70 months; median, 34 months) showed 4 patients dead of disease (10.5, 12, 25, and 64 months after diagnosis), 1 patient alive with extensive metastases (43 months after diagnosis), 1 patient alive with persistent local disease (11 months after diagnosis), and 4 alive without disease (10, 47, 53, and 70 months after diagnosis). One case is too recent for the follow-up. The clinicopathologic and molecular genetic features of rare E-MGNET are essentially identical to those occurring in intestinal locations. Otherwise, typical E-MGNET may harbor EWSR1::PBX1, a finding previously unreported in this tumor type. As in enteric locations, the behavior of E-MGNET is aggressive, with metastases and/or death from disease in at least 50% of patients. E-MGNET should be distinguished from clear cell sarcoma of soft parts and other tumors with similar fusions. ALK expression appears to be a common feature of tumors harboring EWSR1/FUS::ATF1/CREB1 fusion but is unlikely to predict the therapeutic response to ALK inhibition. Future advances in our understanding of these unusual tumors will hopefully lead to improved nomenclature.

Clinical and Pathologic Characterization of 94 Radiation-Associated Sarcomas: Our Institutional Experience.

Radiation-associated sarcomas are an uncommon complication of therapeutic radiation. However, their prevalence has increased with the more widespread use of this treatment modality. The clinical, pathologic and genetic characteristics of radiation-associated sarcomas are not fully understood. In this study we describe the features of 94 radiation-associated sarcomas reviewed at our institution between 1993 and 2018, evaluate their overall survival (OS) and progression-free survival (PFS) outcomes, and compare them with their sporadic counterparts reviewed within the same time period. Histologic subtypes of all radiation-associated sarcomas included 31 (33%) undifferentiated sarcomas, 20 (21%) osteosarcomas, 17 (18%) angiosarcomas, 10 (11%) malignant peripheral nerve sheath tumor (MPNST), 9 (10%) leiomyosarcomas, 4 (4%) myxofibrosarcomas, and 3 (3%) rhabdomyosarcomas. Six patients had a documented cancer predisposition syndrome. The most common preceding neoplasms included adenocarcinoma (47%) and squamous cell carcinoma (19%), with a mean latency of 13 years. Multivariable Cox survival analysis demonstrated that advanced stage at diagnosis based on pT category (AJCC eighth edition) and fragmented resection were associated with worse survival outcomes. In addition, there was a statistically significant difference in PFS between radiation-associated undifferentiated sarcomas and MPNST when compared to their sporadic counterparts using the Kaplan-Meier method and Log-rank analysis. Overall, our study shows that radiation-associated sarcomas comprise a wide clinico-pathologic spectrum of disease, with a tendency for aggressive clinical behavior. This study further delineates the understanding of these uncommon diseases. Future studies are necessary to better understand the genetic and epigenetic changes that drive the differences in behavior between these tumors and their sporadic counterparts, and to offer better treatment options.

What's new in soft tissue and bone pathology 2022-updates from the WHO classification 5th edition.

The 2020 release of the WHO Classification of Soft Tissue and Bone Tumors, 5th edition, contains several changes driven by new knowledge in the field. These include reclassification of some entities, refinement of risk classification systems, and the inclusion of novel disease processes, many of which are driven by recurrent gene fusions. The most notable changes are described here.

Droplet Digital PCR (ddPCR) as a Novel Technology in Detecting CTNNB1 Mutations in Desmoid Fibromatosis.

Desmoid fibromatosis (DF) is a locally aggressive soft tissue neoplasm with frequent recurrences. DF is characterized by alterations in the Wnt/ß-catenin pathway, with the majority showing sporadic mutations in CTNNB1 , whereas others have germline mutations in APC . Immunohistochemical staining for ß-catenin is often difficult to interpret and can be negative in up to 30% of cases. Prior studies have shown that some DFs lacking nuclear expression of ß-catenin may carry activating CTNNB1 mutations. Droplet digital polymerase chain reaction (ddPCR) has been used effectively in detecting mutations in formalin-fixed, paraffin-embedded (FFPE) samples of various cancer types. In this study, we assess the diagnostic utility of ddPCR to detect CTNNB1 mutations in DF with ß-catenin expression on immunohistochemistry (IHC), as well as in diagnostically challenging cases. Of the 28 DFs with nuclear ß-catenin expression by IHC, 24 cases showed a CTNNB1 mutation by ddPCR using primers against the most common point mutations in CTNNB1 . The most frequent mutation was T41A (n=14; 50%), followed by S45F (n=8; 33%) and S45P (n=3;12%). We identified 8 additional (myo)fibroblastic lesions of uncertain classification, which were negative for nuclear ß-catenin expression by IHC. We detected CTNNB1 mutations in 3 unknown lesions, including S45F (n=2) and S45P (n=1). ddPCR is a sensitive, rapid and cost-efficient methodology to detect common CTNNB1 mutations in DF, especially in diagnostically challenging cases.

Prevalence and detection of actionable BRAF V600 and NRAS Q61 mutations in malignant peripheral nerve sheath tumor by droplet digital PCR.

Malignant peripheral nerve sheath tumors ( MPNSTs) are aggressive tumors with poor prognosis that do not typically respond well to standard chemotherapy. Recently, point mutations involving BRAF V600E have been demonstrated in a subset of MPNST, offering the possibility of targeted treatment. However, the reported prevalence of these alterations is variable. Mutations involving NRAS, which is also involved in the MAPK/ERK pathway and amenable to targeted inhibitors, have not been well characterized in MPNST. In this study, we validated droplet digital polymerase chain reaction for the detection of BRAF V600E and NRAS Q61 mutations and evaluate the prevalence of BRAF V600E and NRAS Q61 mutations in 79 cases of MPNST, including 45 sporadic, 27 NF-1 associated, and 7 radiation-associated tumors. We detected actionable BRAF or NRAS mutations in 3 of 44 sporadic MPNSTs (6.8%), including 2 BRAF V600 and 1 NRAS Q61 mutations, as well as 1 NRAS Q61 mutation in a tumor that was ultimately considered to represent melanoma. These 3 cases with positive mutations were exclusively in sporadic, high-grade MPNST (FNCLCC grade 3 of 3), with a prevalence of 11.5% in this group (3.8% NRAS Q61 mutations and 7.7% BRAF V600 mutations). None of the tumors associated with NF-1 or prior radiation had detectable mutations in the genes tested. Overall, the prevalence of these alterations offers the possibility of targeted therapy in this aggressive type of sarcoma and suggests the potential benefit of routine clinical testing.

Tyrosine kinase-altered spindle cell neoplasms with EGFR internal tandem duplications.

In this study, we present two extra-renal pediatric spindle cell neoplasms with epidermal growth factor receptor (EGFR) internal tandem duplications (ITD). Histologically, these tumors demonstrated the same histologic features seen in other tyrosine kinase-altered spindle cell neoplasms, with one case showing abundant adipose tissue with cellular fibrous septae resembling lipofibromatosis and the other case showing fascicles of spindled cells resembling infantile fibrosarcoma. There was variable expression of CD34, S100, and SMA, and all cases were negative for panTRK. This case series adds to our molecular understanding of the spectrum of tyrosine kinase-altered spindle cell neoplasms and represents the first reported examples of EGFR ITDs in extra-renal tumors. The presence of EGFR alterations in the absence of gene fusions represents a potential therapeutic target and necessitates a broader testing panel for this group of tumors.

Fulminant Pyoderma Gangrenosum After Outpatient Knee Arthroscopy.

Pyoderma gangrenosum is an immunologic, ulcerative cutaneous condition often associated with systemic disease and frequently precipitated by trauma. It is noninfectious, but the inflammatory assault can resemble a malignant infection such as necrotizing fasciitis. Despite its clinical resemblance to infection, surgical débridement worsens the condition and may remove morphologic clues to the true disease, thus creating a vicious cycle of surgical débridements and disease progression. Furthermore, diagnostic histopathologic and laboratory features are nonspecific, requiring exclusion of other processes. Therefore, appropriate nonsurgical treatment and immunosuppression are commonly delayed, often at a significant cost to the patient. We present a case of pyoderma gangrenosum occurring after outpatient knee arthroscopy that masqueraded as a postsurgical infection. We discuss the diagnostic approach and how a complex reconstruction involving cartilage restoration and soft-tissue coverage was achieved.

Desmoid-type fibromatosis of the lower extremity: A unique case of complete lesion resolution following core needle biopsy.

Desmoid-type fibromatosis (DF) is a rare neoplasm characterized by fibroblastic and myofibroblastic proliferation. While characterized as a benign lesion that does not metastasize, desmoid-type fibromatosis exhibits a wide range of behavior from aggressive local tissue invasion and post-surgical recurrence to spontaneous regression. Tumor regression can occur following systemic medical therapy or rarely may occur in the absence of therapy. We present a case of a 50-year-old female with a left thigh vastus medialis intramuscular mass which underwent imaging work-up and subsequent core needle ultrasound-guided biopsy showing results of desmoid-type fibromatosis. Following biopsy, the tumor showed prompt, complete regression with complete MRI resolution 2 months following biopsy. The patient showed no evidence of disease recurrence out to one year on MRI surveillance. This case report will discuss desmoid-type fibromatosis imaging features, treatment strategies, spectrum of disease behavior, and atypical behavior such as the spontaneous tumor regression as seen in this case report. To our knowledge there have been no reported cases of DF spontaneous regression 2 months following a core needle biopsy. Understanding the variable behavior of desmoid-type fibromatosis can assist the radiologist in guiding management of these lesions with the goal of optimizing clinical outcomes and preventing unnecessary aggressive treatments for stable or regressing disease.

A Rare Case of Vulvar Hibernoma Treated With Resection.

Hibernoma is a rare benign neoplasm of brown adipose tissue most frequently involving the thigh, shoulder, back, and neck. Differentiating this benign entity from other lipomatous tumors such as well-differentiated liposarcoma is essential, given the different surgical approaches and prognosis associated with each diagnosis. It is helpful for the radiologist to recognize the uncommon locations of hibernoma, as well as characteristic imaging features, in order to properly include it in the differential considerations. Here we present a rare case of symptomatic vulvar hibernoma in a 25-year-old woman treated with surgical excision.

Synovial Sarcoma: A Series of Small Tumors in Active Duty Service Members.

Synovial Sarcoma is a soft tissue sarcoma with a propensity to imitate a benign neoplasm. It is most common in males 15-40 years old, typically presents as a slow growing painful mass, and often arises insidiously without alarm to the patient. Three patients with synovial sarcomas who had each undergone an index procedure to treat a small presumedly benign mass that was later identified as synovial sarcoma were reviewed. All three patients required re-excision of the tumor and tumor bed and are currently undergoing routine surveillance. All patients exhibited the classic translocation t(X;18) (p11.2; q11.2) and all were of the monophasic type. All lesions were less than 35 mm in greatest longitudinal dimension on MRI. None have experienced recurrences of synovial sarcoma to date. Healthcare providers should be aware of the synovial sarcoma's propensity to masquerade as a benign disease and the characteristic clinical and radiological findings. We advocate for a low threshold to obtain advanced imaging and consideration of a tissue diagnosis prior to excision. A referral to an orthopedic oncologist should be considered and biopsy should only be performed where the definitive treatment will take place if malignancy is identified.

Trichobezoar Causing Airway Compromise during Esophagogastroduodenoscopy.

Objectives. (1) Report the case of a 5-year-old female with trichotillomania and trichophagia that suffered airway compromise during esophagogastroduodenoscopy for removal of a trichobezoar. (2) Provide management recommendations for an unusual foreign body causing extubation and partial airway obstruction. Methods. Case report of a rare situation of airway compromise caused by a trichobezoar. Results. A 5-year-old patient underwent endoscopic retrieval of a gastric trichobezoar (hairball) by the gastroenterology service under general endotracheal anesthesia in a sedation unit. During removal, the hairball, due to its large size, dislodged the endotracheal tube, effectively extubating the patient. The bezoar became lodged at the cricopharyngeus muscle. Attempts to remove the bezoar or reintubation were unsuccessful. The child was able to be mask ventilated while the otolaryngology service was called. Direct laryngoscopy revealed a hairball partially obstructing the view of the glottis from its position in the postcricoid area. The hairball, still entrapped in the snare from the esophagoscope, was grasped with Magill forceps and slowly extracted. The patient was then reintubated and the airway and esophagus were reevaluated. Conclusions. Trichobezoar is an uncommon cause of airway foreign body. Careful attention to airway management during these and similar foreign body extractions can prevent inadvertent extubations.

The microcirculation is preserved in emergency department low-acuity sepsis patients without hypotension.

OBJECTIVES: Microcirculatory dysfunction plays an important role in sepsis pathophysiology. Previous studies using sidestream dark-field (SDF) imaging have demonstrated microcirculatory flow abnormalities in patients with septic shock; however, the microcirculation is relatively unstudied in lower-acuity sepsis patients. The hypothesis was that patients with sepsis, but without hypotension, will demonstrate signs of flow abnormalities compared to noninfected control patients. METHODS: This was a prospective, observational study in a convenience sample of patients with sepsis and noninfected controls, conducted in three urban, tertiary care emergency departments (EDs) in the United States. Sepsis was defined as suspected infection plus two or more systemic inflammatory response syndrome (SIRS) criteria; those with hypotension were excluded. Noninfected controls were ED patients without infection and without SIRS criteria. SDF imaging was obtained in all study patients during ED evaluation. Recommended microcirculatory flow parameters were measured, and the difference in these measures between sepsis patients and noninfected controls were calculated. The authors also correlated microcirculatory flow parameters with patient variables, including serum lactate. RESULTS: A total of 106 patients were enrolled: 63 with sepsis and 43 noninfected controls. There were no differences in microcirculatory flow scores between sepsis patients and noninfected controls. Median microvascular flow index (MFI; with interquartile range [IQR] was 3.00 (IQR = 2.73 to 3.00) in sepsis patients versus 2.93 (IQR = 2.73 to 3.00) in control patients (p = 0.33), and mean proportion of perfused small vessels (PPV) was 91.5% (95% CI = 89.7% to 93.3%) versus 91.8% (95% CI = 89.7% to 93.9%), with a mean difference of 0.3% (95% CI = -2.5% to 3.1%; p = 0.84). Similarly, there were no significant differences in total vessel density, perfused vessel density, or heterogeneity index (HI). In the subset of infected patients for whom serum lactates were obtained (n % 37), MFI and PPV were negatively correlated with elevated serum lactate values: r = -0.32, p = 0.04; and r = -0.44, p < 0.01, respectively. CONCLUSIONS: Measureable microcirculatory flow abnormalities were not observed in patients with early sepsis in the absence of hypotension. However, microcirculatory abnormalities were correlated with elevated serum lactate in normotensive sepsis patients, supporting the notion that impaired microcirculatory flow is coupled with cellular distress.

Lung injury prediction score for the emergency department: first step towards prevention in patients at risk.

BACKGROUND: Early identification of patients at risk of developing acute lung injury (ALI) is critical for potential preventive strategies. We aimed to derive and validate an acute lung injury prediction score (EDLIPS) in a multicenter sample of emergency department (ED) patients. METHODS: We performed a subgroup analysis of 4,361 ED patients enrolled in the previously reported multicenter observational study. ED risk factors and conditions associated with subsequent ALI development were identified and included in the EDLIPS model. Scores were derived and validated using logistic regression analyses. The model was assessed with the area under the receiver-operating curve (AUC) and compared to the original LIPS model (derived from a population of elective high-risk surgical and ED patients) and the Acute Physiology and Chronic Health Evaluation (APACHE II) score. RESULTS: The incidence of ALI was 7.0% (303/4361). EDLIPS discriminated patients who developed ALI from those who did not with an AUC of 0.78 (95% CI 0.75, 0.82), better than the APACHE II AUC 0.70 (p ≤ 0.001) and similar to the original LIPS score AUC 0.80 (p = 0.07). At an EDLIPS cutoff of 5 (range -0.5, 15) positive and negative likelihood ratios (95% CI) for ALI development were 2.74 (2.43, 3.07) and 0.39 (0.30, 0.49), respectively, with a sensitivity 0.72(0.64, 0.78), specificity 0.74 (0.72, 0.76), and positive and negative predictive value of 0.18 (0.15, 0.21) and 0.97 (0.96, 0.98). CONCLUSION: EDLIPS may help identify patients at risk for ALI development early in the course of their ED presentation. This novel model may detect at-risk patients for treatment optimization and identify potential patients for ALI prevention trials.

Towards prevention of acute lung injury: frequency and outcomes of emergency department patients at-risk - a multicenter cohort study.

BACKGROUND: Few emergency department (ED) evaluations on acute lung injury (ALI) have been carried out; hence, we sought to describe a cohort of hospitalized ED patients at risk for ALI development. METHODS: Patients presenting to the ED with at least one predisposing condition to ALI were included in this study, a subgroup analysis of a multicenter observational cohort study (USCIITG-LIPS 1). Patients who met ALI criteria within 6 h of initial ED assessment, received end-of-life care, or were readmitted during the study period were excluded. Primary outcome was frequency of ALI development; secondary outcomes were ICU and hospital mortality. RESULTS: Twenty-two hospitals enrolled 4,361 patients who were followed from the ED to hospital discharge. ALI developed in 303 (7.0 %) patients at a median onset of 2 days (IQR 2-5). Of the predisposing conditions, frequency of ALI development was highest in patients who had aortic surgery (43 %) and lowest in patients with pancreatitis (2.8 %). Compared to patients who did not develop ALI, those who did had higher ICU (24 % vs. 3.0 %, p < 0.001) and hospital (28 % vs. 4.6 %, p < 0.001) mortality, and longer hospital length of stay (16 vs. 5 days, p < 0.001). Among the 22 study sites, frequency of ALI development varied from less than 1 % to more than 12 % after adjustment for APACHE II. CONCLUSIONS: Seven percent of hospitalized ED patients with at least one predisposing condition developed ALI. The frequency of ALI development varied significantly according to predisposing conditions and across institutions. Further research is warranted to determine the factors contributing to ALI development.