A Challenging Diagnosis of HHV-8-Associated Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, in a Young Man with Newly-Diagnosed HIV.

BACKGROUND Human herpesvirus-8 (HHV-8)-associated diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), is a rare form of lymphoid malignancy. It poses unique challenges in diagnosis in the setting of human immunodeficiency virus (HIV) infection and concomitant multiorgan dysfunction. CASE REPORT We describe the case of a 26-year-old man who initially presented with pre-syncope and was found to have HIV, with a CD-4 count of 20 cells/µL. His initial clinical presentation was significant for nonspecific symptoms, isolated anemia, and bilateral pleural effusions without gross lymphadenopathy, which was initially attributed to acute HIV infection. However, his hospital course was complicated by anasarca, renal failure, liver dysfunction, pancytopenia, and microscopic hematuria, which required a more comprehensive diagnostic evaluation. Progressive pancytopenia prompted a bone marrow biopsy, which ultimately revealed HHV-8-associated DLBCL, NOS (HDN). We describe his complicated hospital course and eventual diagnosis of HDN. This patient's broad differential diagnoses and overlap among various clinical syndromes posed a significant diagnostic challenge. Additionally, his multiorgan failure limited his treatment options. CONCLUSIONS The management of HHV-8-associated DLBCL, NOS is complex, requiring a multifaceted approach to ensure prompt diagnosis and treatment, especially given difficulty in arriving at an accurate diagnosis due to the significant overlap with other lymphoproliferative disorders and lack of standardized treatment. We highlight the challenges and paucity of data available for management of HDN in the context of a diagnostically challenging case. We discuss the current limitations in diagnosis and treatment of this rare malignancy and the necessity of further investigation, especially in medically complex patients.

Enormous myxoid/round cell liposarcoma: A case report.

Myxoid/round cell liposarcomas (MRCLPS) are a rare soft tissue sarcoma. We report the largest sarcoma in our institutional history. We discuss the patient's surgical management and treatment of the tumor and challenges given its dimensions. Several complications arose following primary resection that were managed by a multidisciplinary team. Although MRCLPS can vary in size, large MRCLPS must be treated cautiously given the potential for complications. Additionally, multidisciplinary treatment of MRCLPS is essential in diagnosing and treating these complex cases.

An Unusual Case of Clear Cell Chondrosarcoma With Early Metastatic Recurrence.

We present a case of a 58-year-old male who presented following 4 months of progressively worsening right upper extremity pain. Initial pathology demonstrated pleomorphic chondroblasts with increased mitotic activity indicating an intermediate grade (Grade 2) clear cell chondrosarcoma of the proximal humerus. Following surgical resection, the primary lesion demonstrated aggressive behavior and early metastasis to the cervical and thoracic spine. The patient unfortunately expired 30 months after initial presentation. Although clear cell chondrosarcoma has been historically regarded as low grade, we present a unique example of an aggressive clinical course of clear cell chondrosarcoma.

Rare Dedifferentiated Periosteal Chondrosarcoma with 11-Year Metastatic Relapse: A Case Report.

A 50-year-old man presented for evaluation of a periscapular mass. Biopsy suggested a low-grade chondrosarcoma; however, the resected specimen revealed a grade 2 chondrosarcoma with a low-grade dedifferentiated mesenchymal component. The mass multiply recurred as chondrosarcoma without a dedifferentiated component before the patient developed lung metastases of chondrosarcoma without a dedifferentiated component 11 years after the initial diagnosis and died of disease. This is one of the first reported cases of a dedifferentiated chondrosarcoma with low-grade dedifferentiated component. While overall prognosis may be better than in typical dedifferentiated chondrosarcoma, this tumor demonstrated numerous local recurrences as well as metastasis.

Neoadjuvant radiation influences the pseudocapsule in soft tissue sarcoma: A histopathologic and radiographic evaluation.

BACKGROUND AND OBJECTIVES: A pseudocapsule surrounds soft tissue sarcoma (STS). Its composition, response to neoadjuvant radiation, and clinical significance are poorly understood. METHODS: Seventeen cases of high-grade undifferentiated pleomorphic sarcoma (UPS) were reviewed, ten of which were treated with neoadjuvant radiation. Magnetic resonance imaging (MRI) studies, pathology slides, and patient records were reviewed. RESULTS: Irradiated pseudocapsules were well-demarcated with fewer viable tumor cells and were thicker on both pathology and MRI measurements when compared to non-irradiated pseudocapsules (p < 0.001, p = 0.04, respectively). Pseudocapsule mean pathology width (MPW) was positively correlated with tumor necrosis percentage (p = 0.044), and negatively correlated with mitotic rate (p = 0.043), though pseudocapsule width measured on MRI did not correlate with these prognostic factors. Despite an evident treatment response to neoadjuvant radiation, viable tumor cells were present within the pseudocapsule and the surrounding healthy tissue. CONCLUSIONS: The pseudocapsule in STS responds to radiation and there appears to be a correlation between pseudocapsule width and tumor necrosis and mitotic activity. As viable tumor cells are present beyond the pseudocapsule, surgeons should remain cautious in determining margins of resection in STS when using the pseudocapsule as a palpable landmark. This novel study is the most detailed to date to describe the histopathologic and radiographic characteristics of the STS pseudocapsule. Further studies are needed to determine the clinical significance of the pseudocapsule.

Characterizing M-protein light chain glycosylation via mass spectrometry.

OBJECTIVES: Monoclonal gammopathy of undetermined significance (MGUS) patients with M-proteins containing n-glycosylated light chains (GLC) have an increased risk for progression to symptomatic plasma cell disorders (PCD). Large-scale research involving the determination of glycan specific moieties is understudied due to the lack of clinically viable methods. This report documents a proof-of-concept glycan characterization method for patients with M-protein GLCs. DESIGN AND METHODS: Twenty-three previously characterized MGUS patients with glycosylated light chains identified by MASS-FIX were used for this study. Glycosylated light chains were enriched from patient serum using light chain (LC) specific Sepharose nanobody beads (NB), followed by glycan digestion via PNGase F. Glycan moieties were derivatized on-target using Girard's reagent T for MALDI-TOF analysis and confirmed with top-down GLC LC-ESI-Q-TOF-MS analysis. RESULTS: Intact GLC LC-ESI-Q-TOF-MS and cleaved glycan MALDI-TOF MS analysis had 100% agreement for the top three intensity glycans between spectra and 88 percent agreement for all reported glycan moieties. GLC moieties among patients were similar with fucosylation being the only notable difference. Additionally, doubly glycosylated light chains were observed in two patients. CONCLUSIONS: The MALDI-TOF method provides the tools to characterize and evaluate GLCs in a clinical setting as it is adaptable to our clinical MASS-Fix assay, relatively cheap, and accurate in glycan moiety assignments as confirmed by top-down GLC LC-ESI-Q-TOF-MS.

Dedifferentiated Chondrosarcoma: A Case Series and Review of the Literature.

Background: Dedifferentiated chondrosarcoma (DCS) is a rare and aggressive malignancy with a poor prognosis. The purpose of this investigation was to describe our treatment and outcomes of 16 DCS patients at our institution and provide a review of the current literature. Methods: This study was a retrospective review over a consecutive twenty-year period. Data including treatment details and outcomes were recorded. Results: A total of 16 cases from 2000 to 2018 were identified. The median age (IQR) was 62 years (52; 69) and the majority of DCS arose in the femur (50%, n=8) and pelvis (25%, n=4). Fourteen (88%) cases underwent limb salvage/wide margin resection (n=13) or intralesional surgery (n=1). For all DCS, the median survival (IQR) was 46 months (12; 140), with both a five and ten-year probability of 32.1% (95% CI, 7.3% to 57.0%). At study conclusion, 81.3% (n=13) were deceased and 18.7% (n=3) were alive. Conclusions: Our findings confirm the poor prognosis of DCS patients, with a five-year estimate of 32%. Together with existing literature, our data might help enable future strategic recommendation of these patients.

Paraganglioma of the Spine: Review of 6 Cases in 20 Years at a Single Institution.

BACKGROUND AND OBJECTIVES: Paragangliomas are rare neuroendocrine tumors that may localize to the spine causing progressive low back pain variably accompanied by radiculopathy. Recurrence, follow-up duration, and role of adjuvant therapy remain unestablished. METHODS: We interrogated our institution's histopathology database for all confirmed cases of spinal paraganglioma between 2000 and 2021. Patient records were retrospectively reviewed to extract diagnostic features, operative treatment, and follow-up outcomes. RESULTS: 6 cases of spinal paraganglioma were surgically treated (67% female vs. 33% male, mean age = 51.3 years). Preoperative symptom duration did not correlate with tumor size (Spearman r = 0.154, P = 0.80). The mean postoperative follow-up duration lasted 3.3 years (range = 2-96 months). There were an equal number of primary and metastatic lesions. 1 tumor exhibited secretory features and was consequently embolized preoperatively. No residual or recurrent disease was evident in the primary cases; however, 2 metastatic cases recurred within 2 years of surgery and 1 patient died. CONCLUSIONS: Given nonspecific clinical and radiologic features, spinal paragangliomas are diagnosed via biopsy or after surgery. Complete surgical resection is often necessary to alleviate symptoms and prevent tumor recurrence. In cases with benign metastases, long-term surveillance is important and adjuvant medical and radiotherapeutic treatment may be beneficial.

Transfusion Independence Achieved with Combination Fedratinib and Luspatercept in an Elderly Man with Heavily Pretreated Intermediate-2 Risk Primary Myelofibrosis.

Myelofibrosis (MF)-associated anemia and transfusion dependency are associated with inferior quality of life and poor prognosis. JAK2 inhibitors and TGF-ß superfamily ligand traps are being explored as treatment options for MF-associated anemia. Here, we present the case of a 66-year-old man with heavily pretreated intermediate-2 (INT-2) risk primary MF who had an exceptional response to combination fedratinib and luspatercept therapy. He achieved transfusion independence and experienced a reduction in spleen size from 20 cm to 12 cm, with remarkable improvement in performance status. Compared with other JAK inhibitors, the mechanism of action of fedratinib may explain its milder effect on anemia. It is possible that the addition of luspatercept may result in an additive or synergistic effect of one or both medications. Although the exact biological pathways have not yet been elucidated, combination fedratinib and luspatercept nevertheless is a promising therapy for anemia in patients with transfusion-dependent INT-2 risk MF.

Does synovial sarcoma grade predict oncologic outcomes, and does a low-grade variant exist?

BACKGROUND AND OBJECTIVES: While historically aggressive, some synovial sarcomas (SS) are clinically indolent. This study sought to determine whether SS grade predicts oncologic outcomes and whether Grade 1 disease might exist. METHODS: Thirty-five cases from 2010 to 2019 were retrospectively reviewed. Clinicopathological data were analyzed and Kaplan-Meier assessed survival. RESULTS: The median patient age was 37 years (interquartile range: 28-51.5). The local control rate was 74.3%, and recurrence-free survival (RFS) was worse in positive versus negative margin resections (p = 0.023). The incidence of metastasis was 21.9% (n = 7) at a median 31 ± 31.7 months, and metastasis-free survival was 50.0% in Grade 3 SS versus 86.5% in Grade 2 (p = 0.026). Among a theoretical Grade 1 group, the overall survival (OS) and RFS profiles were improved compared to Grade 2 and 3 SS, respectively (p = 0.014 and p = 0.030). The Grade 1 group had a 15.8% (n = 3) metastatic rate and 80% 10-year survival. CONCLUSIONS: Tumor grade appears to predict outcomes in SS. A theoretical Grade 1 group showed improved OS and RFS versus Grades 2 and 3 SS, with metastatic rates and long-term survival resembling the historical literature for other low-grade soft tissue sarcomas. Our group continues to support the French Federation of Cancer Centers diagnostic strategy and NCCN treatment guidelines for SS.

An Atypical Adverse Local Tissue Reaction After Ceramic-on-Ceramic Primary Total Hip Arthroplasty.

Adverse local tissue reaction is an uncommon but frequently described complication after total hip arthroplasty (THA). It is most often associated with metal-on-metal hips and less frequently with metal-on-polyethylene implants as part of a mechanically assisted crevice corrosion process. In this report, we describe a rare case of an atypical adverse local tissue reaction in a patient with a ceramic-on-ceramic THA. Abrasive backside liner wear from a prominent screw head, failure of the liner locking mechanism, and liner fragmentation secondary to component-component impingement created an atypical mass and fluid collection leading to THA failure. This case demonstrates the importance of appropriate cup-liner positioning, thorough workup of pain after THA, and the ability of ceramic debris to cause an associated, atypical adverse local tissue reaction.

Pembrolizumab-induced autoimmune haemolytic anemia in a patient with chronic lymphocytic leukaemia successfully treated with ibrutinib.

We present a unique case of a patient with a long-standing history of indolent chronic lymphocytic leukaemia (CLL) who suddenly developed autoimmune haemolytic anaemia after starting immune checkpoint inhibitor therapy for bladder cancer. He had no clear indication to start CLL-directed treatment based on current clinical practice guidelines; however, targeted treatment of CLL with ibrutinib proved to be effective in treating the haemolytic anaemia.

Subdeltoid Rice Bodies in a Patient with Rheumatoid Arthritis on Disease Modifying Antirheumatic Drug Therapy: A Case Report.

CASE: A 58-year-old man with rheumatoid arthritis (RA) on disease modifying antirheumatic drug therapy presented with chronic right shoulder pain. Magnetic resonance imaging was concerning for rice body disease which was confirmed through histology after intraoperative deltoid bursa resection. CONCLUSIONS: Rice bodies can develop regardless of RA symptom severity or the degree of RA medical therapy administered. Therefore, physicians should not disregard rice bodies as a possible cause of symptoms in individuals on appropriate RA medical therapy or who are demonstrating adequate RA symptom and flair control.

The prognostic significance of lymphovascular tumor invasion in localized high-grade osteosarcoma: Outcomes of a single institution over 10 years.

BACKGROUNDS AND OBJECTIVES: Lymphovascular invasion (LVI) has shown evidence of an association with worse survival in high-grade osteosarcoma patients. The purpose of this investigation was to prognosticate LVI as a predictor of survival. METHODS: This was a retrospective review of high-grade, localized osteosarcoma patients over a consecutive 10-year period. Proportional hazards regression was used to identify prognostic factors. Cumulative mortality incidence was estimated with recurrence as a competing risk. RESULTS: Forty-two cases with a median follow-up of 64 months (range, 6-158 months) were reviewed. LVI was present in 21.4% (n = 9) cases. The five- and ten-year survivals in LVI (+) were 40% and 20%, compared to 93% and 81% in LVI (-), respectively (p < .001). After controlling for confounders, advanced age (hazards ratio [HR], 1.134; 95% confidence interval [CI], 1-1.2; p = .01) and LVI (HR, 21.768; 95% CI, 3-135; p = .001) were negative prognosticators. The cumulative incidence of recurrence was no different between LVI (+) and LVI (-) (p = .811), though the incidence of mortality was significantly higher in LVI (+) (p = .003). CONCLUSION: The presence of LVI in the setting of high-grade, localized osteosarcoma is associated with greater rates of mortality and appears to portend a dismal prognosis.

A single institutional experience treating adipocytic tumors: incidence, disease-related outcomes, and the clinical significance of MDM2 analysis.

Adipocytic tumors exist either as a benign or malignant form. The benign variant, lipoma, is composed of normal fat tissue. Lipomas typically develop from superficial fat cells beneath the skin or mucous membranes. Liposarcoma, the malignant counterpart, often develops in deeper tissues and is the most commonly diagnosed Soft Tissue Sarcoma (STS), comprising at least 20% of adult STS. However, malignant tumors of fatty origin exist as a spectrum of diagnoses, each carrying a unique risk of recurrence, metastasis, and longterm survival. The World Health Organization classifies liposarcomas into five categories: i) Atypical Lipomatous Tumors/Well Differentiated (ALT/WD); Ii) Dedifferentiated (ALT/DD); Iii) Myxoid; Iv) Round cell; and v) Pleomorphic. Lipomatous tumors often exhibit different immunohistochemical patterns. Benign lipomas are distinguished by the absence of Murine Double-Minute 2 (MDM2) amplification. Similarly, ALT/WD, classically defined as a low-grade and locally aggressive tumor, demonstrates consistent patterns of MDM2 amplification. Some studies suggest 10% of ALT/WD progress to the highgrade DD form, with others report a dedifferentiation rate of as high as 20% for primary ALT/WD based on location. The ALT/DD subtype is aggressive and has a high capacity to metastasize. While the mechanism of pathogenesis of ALT/DD metastasis is unknown, previous studies suggest that increased MDM2 amplification may play a role. This study sought to evaluate a single institutional experience treating the entire spectrum of lipomatous tumors and describe utilization patterns of MDM2 testing. The group hypothesized: i) Atypical Lipomatous Tumors (ALT), which include ALT/DD and ALT/WD, would exhibit a higher rate of local recurrence than lipomas with no significantly increased incidence of metastases; and ii) at least 50% of our MDM2 testing of ALT would prove positive for the MDM2 overamplification. This study retrospectively reviewed 105 cases (66 lipomas, 27 ALTs, 12 liposarcomas) of patients who underwent lipomatous tumor excision at our institution from 2013 to 2017. Twenty-five tumors (6 lipomas, 18 ALT, 1 liposarcoma) were tested for MDM2 amplification. Three of the tested tumors recurred (2 ALT, 1 liposarcoma), and each exhibited MDM2 overamplification. Five tumors (5 liposarcoma) developed late metastases. These data suggest that although ALT is associated with a higher rate of local recurrence, metastases are quite rare. Additionally, the data demonstrate a high rate of positive MDM2 testing (76%) based on clinical and imaging characteristics of the tumors.

Well-differentiated liposarcoma primary from thymic stroma: Case report and literature review.

Primary liposarcoma of thymic stroma is an exceptionally rare tumor. Histological findings are often definitive for diagnosis, however due to the variability of nuclear atypia and the overlapping with other adipocytic tumors, ancillary techniques are helpful as confirmatory tools. Currently, Fluorescent in situ hybridization for MDM2 is the gold standard for diagnosis of well-differentiated and dedifferentiated liposarcomas, however a panel of immunohistochemical stainings, including MDM2, CDK4 and p16 is available as alternative method, helping to distinguish liposarcoma from its benign counterpart lipoma, especially in borderline cases. We describe the case of a young female diagnosed with a well-differentiated lipomatous tumor primary of thymic stroma with near cut-off result for MDM2-FISHand positive immunohistochemical staining for the panel described above. We discuss the challenges in the diagnosis of this rare entity andpresent an updated literature review.

Orbital Mucosa-Associated Lymphoid Tissue Lymphoma and Primary Cutaneous Classical Hodgkin Lymphoma: A Rare Case Report and Review of the Literature.

A 60-year-old woman was diagnosed with isolated mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexa and treated with two years of weekly rituximab for eight doses followed by rituximab maintenance. After nearly two years of maintenance therapy, she developed a tender, indurated mass on the left neck. Biopsy results were consistent with primary cutaneous classical Hodgkin lymphoma (PCCHL).