Giant Cell Tumor Research Articles

Validity of the Musculoskeletal Tumor Society Score for lower extremity in patients with bone sarcoma or giant cell tumour of bone undergoing bone resection and reconstruction surgery in hip and knee

BackgroundThe Musculoskeletal Tumor Society Score (MSTS) is widely used to evaluate functioning following surgery for bone and soft-tissue sarcoma. However, concerns have been raised about its content validity due to the lack of patient involvement during item development. Additionally, literature reports inconsistent results regarding data quality and structural validity. This study aimed to evaluate content, structural and construct validity of the Danish version of the MSTS for lower extremity (MSTS-LE).MethodsThe study included patients from three complete cohorts (n = 87) with bone sarcoma or giant cell tumour of bone who underwent bone resection and reconstruction surgery in hip and knee. Content validity was evaluated by linking MSTS items to frameworks of functioning, core outcome sets and semi-structured interviews. Data quality, internal consistency and factor analysis were used to assess the underlying structure of the MSTS. Construct validity was based on predefined hypotheses of correlation between the MSTS and concurrent measurements.ResultsContent validity analysis revealed concerns regarding the MSTS. The MSTS did not sufficiently cover patient-important functions, the item Emotional acceptance could not be linked to the framework of functioning, the items Pain and Emotional acceptance pertained to domains beyond functioning and items’ response options did not match items. A two-factor solution emerged, with the items Pain and Emotional acceptance loading highly on a second factor distinct from functioning. Internal consistency and construct validity showed values below accepted levels.ConclusionThe Danish MSTS-LE demonstrated inadequate content validity, internal consistency, and construct validity. In addition, our analyses did not support unidimensionality of the MSTS. Consequently, the MSTS-LE is not a simple reflection of the construct of functioning and the interpretation of a sum score is problematic. Clinicians and researcher should exercise caution when relying solely on MSTS scores for assessing lower extremity function. Alternative outcome measurements of functioning should be considered for the evaluation of postoperative function in this patient group.

Plexiform Variant of Ameloblastoma in Body of Mandible: Case Report and Review of Literature

Ameloblastoma is a benign but locally aggressive odontogenic epithelial neoplasm arising from remnants of dental lamina and dental organ [1,4]. This neoplasm is more prevalent between 2nd to 4th decade of life and mandible (11%) is more commonly involved than maxilla (1%) [2,5]. It has an aggressive behavior and recurrent course, It is rarely metastatic. Ameloblastoma represents 10% of odontogenic tumors and 1% of all tumors and cysts involving the maxillo mandibular region [1]. The World Health Organization (WHO) classification of 2017 describes ameloblastomas of the following four types: Solid/multicystic ameloblastoma (91%) unicystic ameloblastoma (6%); extraosseous/peripheral ameloblastoma (2%); and metastasizing ameloblastoma (1%). [3,8] A conclusive diagnosis can only be made by histopathology because it has wide range of histologic patterns and has radiographic characteristics with other lesions such the odontogenic keratocyst, giant cell tumour, aneurysmal bone cyst, and renal cell carcinoma metastasis.[5] Treatment for each type of ameloblastoma differs depending on its biological behaviour and rate of recurrence. This report presents a case of ameloblastoma involving the body of mandible with resorption of the root apices of canine, premolars and first molar. The lesion extends till the base of mandible with intact lower border. This was surgically excised preserving the lower border of mandible with safe sound margins of bone.

TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Benign bone tumors in North East Indian population – A hospital-based study

Background: Primary bone tumors are relatively uncommon and constitute only 0.2–0.5% of all tumors in all ages in most series reported worldwide. Benign bone tumors are more common than the malignant bone tumors. Not many studies on benign bone tumors in the North Eastern Indian population are published in the available literature. Aims and Objectives: The current study was done with the aim to find out the epidemiological data on benign bone tumors in patients of the North-East Indian population who were admitted to the orthopedic department of a teaching institute. Materials and Methods: A hospital-based retrospective study with prospective effect was conducted on benign bone tumors in patients admitted to the Department of Orthopedics at our teaching institute from 2016 to 2020. Patients of all ages and both sexes with suspicion of bone tumors based on history and clinical examination were subjected to roentgenographic evaluation, including computed tomography (CT) scan and/or magnetic resonance imaging. Pre-operative core needle biopsy under C-arm/CT guidance or incisional biopsy was done for histological diagnosis, followed by appropriate intervention. Soft-tissue tumors and malignant bone tumors were excluded. Patients were followed up for recurrence, complications, and functional recovery. Results: Forty patients of bone tumors were treated out of 2288 patients admitted to the department (incidence of 1.75%). 29 were benign bone tumors with an incidence of 1.27%. Of 10–20 years age group was most commonly affected. Male preponderance with M: F=6.25:1. Femur (n=16) was the most commonly affected bone. Presenting features were swelling (n=18), pain (n=11), and pathological fracture (n=5). osteochondroma (n=15) was most common followed by giant cell tumor of bone (n=6). Treatment ranged from intralesional steroid to wide marginal excision based on histopathological diagnosis, the extent of tumor, anatomical location, and presenting symptoms. All patients were rehabilitated to activities of daily living at the final follow-up. No recurrence or any long-term complications were reported. Conclusion: This study gives epidemiological data on benign bone tumors, which can be used for setting up or upgrading dedicated oncological or oncosurgery institutes. A multicentric study on a large population in the future is suggested to obtain a larger data bank.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Deep learning-based detection of primary bone tumors around the knee joint on radiographs: a multicenter study.

Most primary bone tumors are often found in the bone around the knee joint. However, the detection of primary bone tumors on radiographs can be challenging for the inexperienced or junior radiologist. This study aimed to develop a deep learning (DL) model for the detection of primary bone tumors around the knee joint on radiographs. From four tertiary referral centers, we recruited 687 patients diagnosed with bone tumors (including osteosarcoma, chondrosarcoma, giant cell tumor of bone, bone cyst, enchondroma, fibrous dysplasia, etc.; 417 males, 270 females; mean age 22.8±13.2 years) by postoperative pathology or clinical imaging/follow-up, and 1,988 participants with normal bone radiographs (1,152 males, 836 females; mean age 27.9±12.2 years). The dataset was split into a training set for model development, an internal independent and an external test set for model validation. The trained model located bone tumor lesions and then detected tumor patients. Receiver operating characteristic curves and Cohen's kappa coefficient were used for evaluating detection performance. We compared the model's detection performance with that of two junior radiologists in the internal test set using permutation tests. The DL model correctly localized 94.5% and 92.9% bone tumors on radiographs in the internal and external test set, respectively. An accuracy of 0.964/0.920, and an area under the receiver operating characteristic curve (AUC) of 0.981/0.990 in DL detection of bone tumor patients were for the internal and external test set, respectively. Cohen's kappa coefficient of the model in the internal test set was significantly higher than that of the two junior radiologists with 4 and 3 years of experience in musculoskeletal radiology (Model vs. Reader A, 0.927 vs. 0.777, P<0.001; Model vs. Reader B, 0.927 vs. 0.841, P=0.033). The DL model achieved good performance in detecting primary bone tumors around the knee joint. This model had better performance than those of junior radiologists, indicating the potential for the detection of bone tumors on radiographs.

Comprehensive Molecular Characterization of a Large Series of Calcified Chondroid Mesenchymal Neoplasms Widening Their Morphologic Spectrum.

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed whole-exome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Extra-articular tenosynovial giant cell tumor with novel FBN1::CSF1 fusion masquerading as a floor of mouth inflammatory process

Malignant Phyllodes Tumour with Heterologous Osteosarcomatous differentiation and Osteoclast-like giant cells: Case Report of an uncommon neoplasm

Background: Phyllodes tumour (PT), an uncommon fibroepithelial neoplasm accounts for less than 1% of all primary tumours of the breast. MPT with osseous differentiation often gets misdiagnosed on imaging as benign giant calcifications resulting in treatment delay. We describe a rare case of MPT with heterologous osteosarcomatous differentiation and osteoclast-like giant cells and review the literature to discuss clinical-radiological findings, differential diagnosis and treatment options. Case Presentation: A 34-year-old female presented with a right breast lump. Mammography showed a high-density irregular mass with amorphous dense calcification, suggesting neoplastic aetiology. Preoperative core needle biopsy raised the possibility of a phyllodes tumour versus giant cell tumour. Wide local excision was performed to confirm the diagnosis which revealed the presence of a biphasic tumour with osteoid-like matrix and numerous osteoclastic giant cells. Immunohistochemistry was used to rule out metaplastic carcinoma or carcinosarcoma. The stromal cells were negative for panCK and P63 and positive for vimentin, CD10 and BCL-2. The osseous component was positive for Osteonectin and SATB2. Thus, a final diagnosis of malignant phyllodes tumour with heterologous osteosarcomatous differentiation and osteoclast-like giant cells was made. Conclusion: MPT with osteosarcomatous differentiation is a rare and challenging entity associated with a poor clinical outcome. Accurate diagnosis requires a multidisciplinary approach involving breast surgeons, pathologists and radiologists with careful histopathological examination. Wide local excision with close surveillance is crucial for timely detection of tumour recurrence and metastasis.

Study of Multimodality Imaging Features of Brown Tumor or Osteitis Fibrosa Cystica

Introduction Brown tumor, also known as osteitis fibrosa cystica, is a rare but significant manifestation of hyperparathyroidism characterized by focal bone lesions resulting from excessive osteoclastic activity. Despite its rarity, Brown tumor poses diagnostic challenges due to its varied clinical presentations and radiographic features, often mimicking other bone lesions such as giant cell tumors or metastatic disease. Material and Methods In this study, we present a retrospective analysis of 6 cases of Brown tumor diagnosed and managed at our institution over a 12 months period from April 2022 to April 2023. Our objectives are to delineate the diverse clinical manifestations of Brown tumor, discuss diagnostic modalities utilized, treatment strategies employed, and evaluate patient outcomes. Results Five out of our six patients were females. Also 5 out of our 6 patients were under the age of 25. 2 patients presented to us with multiple lytic lesions and other 4 patients had solitary lesions. 1 patient out of 6 presented to us with pathological fracture. Only 2 out of the 6 patients had a positive sestamibi scan but Ultrasonography (USG) of the neck and MRI of the neck showed the presence of parathyroid adenoma in all the cases. Preoperative average of VAS score in this patients was 67 which was decreased to as low as 24. We performed paired t-tests on the blood investigation values and Visual Analog Scale (VAS) scores for all patients. The results were statistically significant, with values returning to normal three months post-surgery. Conclusion When radiographic evidence of a lytic lesion and hypercalcemia are present, Brown tumor should always be considered in the differential diagnosis. Brown tumor has a distinctive imaging appearance, with solid components displaying intermediate to low intensity on T1- and T2-weighted images, while the cystic components appear hyperintense on T2-weighted images and exhibit fluid-fluid levels. MRI of the neck corroborates the ultrasound findings and detects parathyroid adenomas as hyperintense nodes on T2-weighted images. Parathyroidectomy yields excellent results, enabling conservative management of lytic lesions.

Childhood Tumors around the Knee Revisited: Predilection Sites for Most Entities Confirmed.

Background: The diagnostic work-up of musculoskeletal tumors is a multifactorial process. During the early phase, differential diagnoses are made using basic radiological imaging. In this phase, part of the decision making is based on the patient's age, as well as the incidence and predilection sites of different entities. Unfortunately, this information is based on older and fragmented data. In this study, we retrospectively evaluated all soft-tissue and bone tumors around the knee in children treated at our tertiary center in the last 20 years, with the aim of verifying the data used today. Methods: In this retrospective study, the databank of our tertiary center was used to give an overview of treated tumors around the knee in children. Results: We were able to include 224 children with bone and soft-tissue tumors around the knee. The cohort consisted of 184 bone tumors, of which 144 were benign and 40 malignant. The 40 soft-tissue tumors comprised 30 benign and 10 malignant masses. The most common lesions were osteochondromas (88) in the bone and tenosynovial giant-cell tumors (12) in the soft tissue. Conclusions: With this original work, we were able to verify and supplement earlier studies, as well as deepen our insight into these very rare diseases.

Free-hand ultrasound strain elastography in evaluation of soft tissue tumors.

The purpose of this study is to evaluate elastography in a wide spectrum of soft tissue superficial lesions by correlating the elastographic characteristics of these lesions with the elastographic score (ES) system established by Asteria. Forty patients with different superficial lesions of the soft tissues were studied, including lipomas, schwannomas, neuromas, epidermal inclusion cysts, "in transit" melanoma metastasis, arterio-venous malformation, and giant-cell tumor. An ultrasound examination was performed combined with color-Doppler and elastographic module. The B-mode criteria were echogenicity, margins, and structural homogeneity of the lesion. The color-Doppler criterion was irregular and mainly intra-nodular vascularization. ES 1-4 was attributed, in relation with the increasing tissue stiffness, according to the classification of Asteria adapted for soft tissues. Subsequently, we added to each single B-mode and color-Doppler criterion the ES 3 and 4, thus crossing two parameters of malignancy. All the presumptive diagnoses formulated were confirmed with the clinical data or with the histopathological result. The hypoechoic appearance had the best diagnostic performance. Sensitivity was 87%, specificity 71%, positive predictive value (PPV) 80%, negative predictive value (NPV) 80%, and diagnostic accuracy 80%. There was a good correlation with the clinical and biopsy data, the irregularity of margins the worst performance, the inhomogeneity an intermediate. Color-Doppler had sensitivity 74%, specificity 82%, PPV 85%, NPV 70% and diagnostic accuracy 77.5%. Elastography had sensitivity 87%, specificity 94%, PPV 95%, NPV 84%, and diagnostic accuracy 90%. The combination hypoechoic appearance + ES3/ES4 showed sensitivity 83%, specificity 100%, PPV 100%, NPV 81%,and diagnostic accuracy of 90%. The combination of irregularity of margins + ES3/ES4 showed sensitivity 43%, specificity 100%, PPV 100%, NPV 59%, and diagnostic accuracy of 67.5%. The combination of inhomogeneity of the lesion + ES3/ES4 showed sensitivity 65%, specificity 94%, PPV 94%, NPV 68%, and diagnostic accuracy of 78%. The combination of the color-Doppler with the ES3/ES4 showed sensitivity 69.5%, specificity 100%, PPV 100%, NPV 71%, and diagnostic accuracy of 82.5%.In the combined evaluation, there was a significant increase in specificity, allowing healthy subjects to be categorized as correctly negative, with a reduction in false positives which also translates into an increase in PPV. Elastography alone is not sufficient for a correct diagnostic classification and must be considered as an additional parameter in the study of soft-tissue lesions. Although there was a good agreement between B-mode malignancy criteria and ES3/ES4, there is no significant improvement in sensitivity. Ultrasound assessment, especially of superficial lesions, cannot be separated from an integrated approach that foresees the additional and routine use of the elastographic examination.

Giant Cell Tumor of the Rib: A Report of Two Patients.

Giant cell tumor of the bone is a locally aggressive and rarely metastasizing tumor that typically affects the ends of long bones. Less than 1% of giant cell tumor of bone occur in the ribs. Our patients were a 32-year-old woman and a 45-year-old man and were detected following chest traumas. No bone alterations were detected in radiological studies performed immediately after local trauma. Six- and one- months, respectively, following chest trauma, both giant lytic heterogeneous masses arising on an anterior rib arc were radiologically observed. In the computerized tomography-guided needle biopsy, giant cell tumor of bone were diagnosed. Both tumors were completely removed by bloc resection including the adjacent ribs and posterior reconstruction were performed. One patient was preoperatively treated with denosumab. Neither local recurrences nor metastasis have been detected in follow-up. Despite its low frequency and its low degree of suspicion, giant cell tumor of bone should be included in the differential diagnosis of a rapid growing chest mass.

A rare case of giant cell tumor in navicular bone: a case report

A rare case of giant cell tumor in navicular bone: a case report

The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment

BackgroundCurrently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness.MethodsWe conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness.ResultsLow TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS.ConclusionThe results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.

Benign metastasizing tumor or benign epithelial inclusion in the node: A diagnostic dilemma

Generally metastasis implies malignancy, but there are some benign tumours which can also metastasize to lymph nodes, bone, and kidney. The benign tumours which can metastasize includes pleomorphic adenoma, leiomyoma, giant cell tumour of bone and meningioma. A 27 years old female presented to the cytology clinic with the submandibular swelling for past 3 months. Patient is a known case of pleomorphic adenoma post-surgery in the same region 6 years back. On examination two nodular swelling each measuring 1 x 1 which is firm mobile near scar site and left level III lymph node region. A non-guided fine needle aspiration cytology was performed from both the swelling. The Papanicolaou- and May-Grünwald Giemsa-stained smears from both sites showed features of pleomorphic adenoma. The interesting aspect of this article is cytological diagnosis of benign pleomorphic adenoma metastasizing to lymph nodes which is a rare entity.

GIANT CELL TUMOUR OF TENDON SHEATH IN THE FOOT: A RARE CASE REPORT

Giant cell tumor of the tendon sheath (GCT-TS) is predominantly encountered in the hand, ranking as the second most common solid tumor after ganglion cysts. Contrary to its prevalence in the upper extremity, GCT-TS manifestation in the foot is exceptionally rare. This report delineates a unique presentation of GCT-TS in the foot of a 25 y old female, who presented with a painful, progressively enlarging mass in the lateral aspect of her foot. This case underscores the diagnostic challenges and therapeutic considerations in managing such an atypical presentation of GCT-TS.

ISLET-1 expression in soft tissue neoplasms reveals high sensitivity but moderate specificity for desmoplastic small round cell tumors and potential utility as a diagnostic biomarker

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56y). They predominantly affected the upper lobes and measured 1.3 to 9cm in greatest diameter (mean: 4.6cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

Giant cell tumor arising in a cesarean scar: Addition to diagnostic dilemmas.

Giant cell tumor arising in a cesarean scar: Addition to diagnostic dilemmas.