Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:The pathogenesis of dedifferentiated chondrosarcoma is controversial, and no genetic abnormality has consistently been identified in the disease. Focusing on the diagnostic challenges encountered in dedifferentiated chondrosarcoma, the following review aims at summarizing the tumor's active neoplastic pathways while highlighting therapeutic modalities that could potentially be explored to enhance patient survivorship. RECENT FINDINGS/RESULTS:Owing to the challenging examination of small needle biopsy sampling as well as the disease's overlapping morphological and immunohistochemical features with other bone and soft-tissue sarcomas, the diagnosis of dedifferentiated chondrosarcoma can be problematic. While combined doxorubicin- and cisplatin-based regimens remain the first-line systemic chemotherapy in the disease, ~50% of tumors carry EXT1/2 or IDH1/2 mutations, advancing EXT or IDH inhibitors as potential alternative therapies, respectively. Despite systemic chemotherapy, dedifferentiated chondrosarcoma remains an aggressive tumor with dismal prognosis and limited survival. A multidisciplinary collaboration across multiple cancer centers is warranted to yield an accurate diagnosis, understand the disease's underlying pathogenesis, develop adequate treatment, and improve patient survivorship.

Ca2+ signals regulate the function of many immune cells and promote immune responses to infection, cancer, and autoantigens. Ca2+ influx in immune cells is mediated by store-operated Ca2+ entry (SOCE) that results from the opening of Ca2+ release-activated Ca2+ (CRAC) channels. The CRAC channel is formed by three plasma membrane proteins, ORAI1, ORAI2, and ORAI3. Of these, ORAI1 is the best studied and plays important roles in immune function. By contrast, the physiological role of ORAI3 in immune cells remains elusive. We show here that ORAI3 is expressed in many immune cells including macrophages, B cells, and T cells. To investigate ORAI3 function in immune cells, we generated Orai3-/- mice. The development of lymphoid and myeloid cells in the thymus and bone marrow was normal in Orai3-/- mice, as was the composition of immune cells in secondary lymphoid organs. Deletion of Orai3 did not affect SOCE in B cells and T cells but moderately enhanced SOCE in macrophages. Orai3-deficient macrophages, B cells, and T cells had normal effector functions in vitro. Immune responses in vivo, including humoral immunity (T cell dependent or independent) and antitumor immunity, were normal in Orai3-/- mice. Moreover, Orai3-/- mice showed no differences in susceptibility to septic shock, experimental autoimmune encephalomyelitis, or collagen-induced arthritis. We conclude that despite its expression in myeloid and lymphoid cells, ORAI3 appears to be dispensable or redundant for physiological and pathological immune responses mediated by these cells.

Objective/UNASSIGNED:Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). Case Report/UNASSIGNED:A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level, <8 (18-72) pg/mL; (4) 24-hour urine phosphorus level, 0.5 (0.3-1.3) g; and (5) fibroblast growth factor 23 levels, 1241 (reference range, <180) RU/mL. The patient became pregnant, and at term, a cesarean delivery was performed. Ga-68 DOTATATE PET/MRI showed a 9-mm intracortical mass in the right fibular head and right femoral and bilateral calcaneal stress fractures. The fibular lesion was resected; pathology showed a 1.5-cm lesion with positive fibroblast growth factor receptor 1 staining. Discussion/UNASSIGNED:This patient with TIO had an uneventful pregnancy and delivery. TIO is typically caused by benign mesenchymal tumors. Ga-68 DOTATATE PET/computed tomography has been used for localizing tumors causing TIO, yet MRI has superior contrast resolution over computed tomography. Therefore, it is not surprising that Ga-68 PET/MRI successfully localized this patient's tumor to the intracortical space of the fibular head and distinguished it from insufficiency fractures. Conclusion/UNASSIGNED:To our knowledge, this is the first report of phosphate treatment in a pregnant patient with TIO and the first report of a tumor-inducing TIO being localized by Ga-68 DOTATATE PET/MRI.

OBJECTIVES/OBJECTIVE:To evaluate whether a follow-up magnetic resonance imaging (MRI) scan performed after initial ultrasound (US) to evaluate soft tissue mass (STM) lesions of the musculoskeletal system provides additional radiologic diagnostic information and alters clinical management. METHODS:A retrospective chart review was performed of patients undergoing initial US evaluations of STMs of the axial or appendicular skeleton between November 2012 and March 2019. Patients who underwent US examinations followed by MRI for the evaluation of STM lesions were identified. For inclusion, the subsequent pathologic correlation was required from either a surgical or image-guided biopsy. Imaging studies with pathologic correlations were then reviewed by 3 musculoskeletal radiologists, who were blinded to the pathologic diagnoses. The diagnostic utility of MRI was then assessed on the basis of a 5-point grading scale, and inter-reader agreements were determined by the Fleiss κ statistic. RESULTS:Ninety-two patients underwent MRI after US for STM evaluations. Final pathologic results were available in 42 cases. Samples were obtained by surgical excision or open biopsy (n = 34) or US-guided core biopsy (n = 8). The most common pathologic diagnoses were nerve sheath tumors (n = 9), lipomas (n = 5), and leiomyomas (n = 5). Imaging review showed that the subsequent MRI did not change the working diagnosis in 73% of cases, and the subsequent MRI was not considered to narrow the differential diagnosis in 68% of cases. There was slight inter-reader agreement for the diagnostic utility of MRI among individual cases (κ = 0.10) between the 3 readers. CONCLUSIONS:The recommendation of MRI to further evaluate STM lesions seen with US frequently fails to change the working diagnosis or provide significant diagnostic utility.

There are few reported cases of non-Hodgkin's lymphoma metastasis to bone in the lower extremities. The authors present a case of cutaneous B-cell lymphoma thought to be in remission, with metastasis to the first metatarsal head with involvement in the synovial tissue of the first metatarsophalangeal joint. Following excision of the lesion, no further treatment was determined to be necessary. The patient was to be observed for local recurrence.

To the best of the authors' knowledge, this is the first published case of monophasic synovial sarcoma (SS) initially diagnosed as Ewing's sarcoma (ES), yet successfully treated with chemotherapy in a 24-year-old patient. The initial diagnosis showed a monotonous round cell tumor and positivity for CD99, characteristic of ES; however, the cytology was negative for the classic EWSR1 rearrangement of ES. The patient was treated with the standard chemotherapy protocol of ES - COG AEWS1031 Regimen A with vincristine, doxorubicin, cyclophosphamide, and mesna - as well as with wide resection. Post-resection tissue submission showed additional morphologic features which led to a re-evaluation of the classification of the tumor as well as additional molecular studies; these revealed positivity for translocations of SS18 (18q11.1) in 100% of the nuclei, which is most characteristic of SS, thus, reclassifying the neoplasm as a SS tumor. This case underscores the importance of considering several pathologic entities in the differential diagnosis of small, round blue cell tumors, including ES, SS, and lymphoma. It also demonstrates the importance of using chromosomal identification for a more definitive diagnosis, rather than relying on histological features and markers which are found in more than one tumor classification. There is conflicting evidence of the impact of chemotherapy on survival in SS, as it is primarily treated with radiation therapy. Since SS is rare, prospective studies on the effect of chemotherapy on survival are limited in number. However, our case study demonstrates that chemotherapy is another modality that can be used in the treatment of SS neoplasms.

Ultrasound-guided hookwire localization was initially introduced to facilitate the excision of nonpalpable breast lesions by guiding surgical exploration, thereby reducing operative time and morbidity. The same technique has since found utility in a range of other applications outside breast and can be useful within the musculoskeletal system. Despite this, there remains limited literature with respect to its technical aspects and practical utility. We describe our technique and a series of preoperative ultrasound-guided wire localizations in the musculoskeletal system to assist surgical excision of 4 soft tissue masses.

Thus far, only a single case describing an atypical appearance of elastofibroma dorsi at a prior thoracotomy site has been published in the literature. We describe a series of three cases recently imaged at our institution with the same atypical appearance, in order to highlight and increase recognition of this more unusual morphology in post-operative patients.

Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.

Here we present a case of a 38 year old male with an incidentally found right upper lobe lung mass. The patient underwent thoracoscopic resection of the mass which revealed a myxoid spindle cell lipoma. This is an exceedingly rare location for this tumor biology and here we discuss its pathological features and treatment options.