Global Assessment of IRF8 as a Novel Cancer Biomarker

Interferon regulatory factor 8 (IRF8) is a member of the IRF family that is specific to the hematopoietic cell and is involved in regulating the development of human monocytic and dendritic-lineage cells, as well as B cells. Since its utility as a sensitive and specific monoblast marker in the context of acute monocytic leukemias has been recently demonstrated, we hypothesized that it may also be useful as a novel immunohistochemical marker in myeloid sarcomas and blastic plasmacytoid dendritic cell neoplasms (BPDCN) with respect to their differential diagnoses. In this retrospective study, we analyzed the IHC expression pattern of IRF8 in 385 patient samples across 30 types of cancers, referenced to their mRNA expression data available through TCGA. In addition, we assessed IRF8 in 35 myeloid sarcomas, and 13 BPDCNs. Twenty-four of 35 cases of myeloid sarcomas (68.5%) showed positivity for IRF8, with six cases (17.1%) demonstrating IRF8 expression in the absence of CD34 and MPO. All 13 of 13 BPDCNs (100%) showed strong uniform expression of IRF8 and was occasionally more definitive than CD123. IRF8 was negative in all desmoplastic small round cell tumors, Ewing sarcomas, synovial sarcomas, and undifferentiated pleomorphic sarcomas, as well as all epithelial malignancies tested except for 2 triple negative breast cancers that showed subset weak staining. In conclusion, IRF8 is a novel marker helpful in identifying extranodal hematopoietic tumors that can otherwise be difficult to diagnose given the broad differential diagnoses and frequent loss of more common lineage-defining markers.

Cytology of Undifferentiated Round-Cell Sarcomas of Bone and Soft Tissue: Ewing Sarcoma or Not Ewing Sarcoma , That Is the Question

<b><i>Background:</i></b> Undifferentiated round-cell sarcomas (URCSs) of soft tissue and bone are a group of clinically heterogeneous tumors. Diagnosis of these malignancies is based mainly on recurrent genetic alterations. The most common and the best known representative of this group is Ewing sarcoma (ES) which is characterized by gene fusions including EWSR1 or FUS and ETS transcription factors family. Other newly described entities are CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and round-cell sarcoma with EWSR1-non-ETS fusions. All these novel tumors are known as Ewing-like sarcomas. <b><i>Summary:</i></b> It is believed that morphologic features of ES and Ewing-like sarcomas vary only slightly or even that cytomorphology is not relevant. But differences are usually obvious, and some cytologic findings, such as spindle cells, connective tissue fragments, or myxoid stroma, are typical for Ewing-like sarcomas but not for ES. Each of these entities is also characterized by different immunoprofiles. The aim of this review was to summarize cytomorphologic and immunohistochemical features of URCS and compare them with other small round-cell tumors. <b><i>Key Messages:</i></b> Cytology can be successfully used in URCS diagnosis as a complementary tool for core-needle biopsy or even alone in selected cases, especially in recurrent and metastatic tumors. Knowing the morphologic and immunohistochemical differences between URCS is essential to provide appropriate ancillary studies and make a definitive diagnosis.

A Review of Effusion Cytomorphology of Small Round Cell Tumors

<b><i>Background:</i></b> Small round cell tumors (SRCTs) are a broad category of diverse malignant tumors composed of monotonous undifferentiated cells. Involvement of serous fluids by SRCT is rare; however, the identification of exfoliated malignant cells is a crucial component of management and has significant implications for treatment and prognosis. The most common effusion tumors with SRCT morphology include Ewing sarcoma, synovial sarcoma, rhabdomyosarcoma (RMS), small-cell neuroendocrine carcinoma (SCNC), and desmoplastic SRCT, and the cytomorphologic distinction between these tumors is challenging. The purpose of this article is to describe the morphologic features of the most common SRCT in fluids and propose helpful ancillary testing. <b><i>Summary:</i></b> Effusion SRCTs display similar primitive and undifferentiated morphologic features although each has subtle variations. Ewing sarcoma is a mesenchymal neoplasm and harbors characteristic translocations t(11;22) (<i>EWSR1-FLI1</i>) or t(21;22) (<i>EWSR1-ERG</i>). In fluids, Ewing sarcoma shows poorly differentiated cells of variable size with round to oval nuclei, prominent nucleoli, and scant cytoplasm. In contrast, synovial sarcoma typically involves extremities and expresses a fusion transcript in t(X;18) (<i>SS18-SSX</i>). This soft tissue neoplasm demonstrates uniform cells with irregular nuclear contours, characteristic nuclear folding, and scant cytoplasm. RMS is a neoplasm arising from skeletal muscle, and the alveolar subtype demonstrates a translocation in t(2;13) (<i>PAX3-FOXO1</i>). The malignant cells show a spectrum of small round cells and pleomorphic large cells with rhabdoid morphology. RMS cells characteristically express myogenin and MyoD1, markers of skeletal muscle differentiation. Although SCNC is not a classic SRCT, the morphology is similar. SCNC demonstrates tight clusters of malignant cells with nuclear molding and salt-and-pepper chromatin. This tumor classically has neuroendocrine differentiation and is positive for synaptophysin and chromogranin on immunohistochemistry. And last, desmoplastic SRCT typically presents as an intra-abdominal mass in young men and characteristically harbors the translocation t(11;22) (p13;q12) (<i>EWSR1-WT1</i>). Cytomorphologically, the tumor shows small monomorphic cells occasionally arranged as rosette-like structures. <b><i>Key Message:</i></b> The diagnosis of SRCT can be made in effusion samples and is best achieved with a combination of morphologic features, clinical history, and ancillary testing.

Differential diagnosis and treatment of rare forms of primary peritoneal tumors – solitary fibrous and desmoplastic small round cell tumors

Solitary fibrous tumor and desmoplastic small round cell tumor are primary peritoneal malignant tumors. Despite their morphological differences, these diseases are united by low morbidity, the lack of pathogenic symptoms, similar radiological signs, and scant knowledge of prognostic factors. Considering the low morbidity, reliable differential diagnostic signs have not been established at present, which greatly complicates the timely formulation of the diagnosis. On the contrary, cases of choosing the wrong treatment tactics and the lack of a unified management algorithm are increasingly being identified. Radiation and instrumental diagnostic methods such as computed tomography, magnetic resonance imaging, laparoscopy are crucial in determining the extent of the tumor, it is necessary to take into account the biological characteristics of the tumor (morphological type), which affect the nature of tumor growth. With a solitary fibrous tumor and a desmoplastic small-round cell tumor, the computed tomography picture is characterized by the presence of isolated nodular formations in any part of the abdominal cavity, which can also be accompanied by a large omentum, ascites, an increase in retroperitoneal lymph nodes, and distant metastasis to the lungs and bones is possible. In general, the main task of diagnosing a primary peritoneal neoplasm is to take sufficient quality biological material, with the leading role in the diagnosis being given to histological and immunohistochemical studies. On the other hand, the independent experience of many clinics does not exceed single surveillance. This information does not allow doctors to confidently navigate the problem; accordingly, there is a need for multicenter and, possibly, prospective, randomized scientific research in order to develop a unified algorithm for managing patients with primary peritoneal tumors. The approaches to the treatment of these tumors are currently not standardized and not well studied due to the rarity of the pathology. According to the available information, the treatment of desmoplastic small round cell tumors is based on multimodal therapy, including systemic chemotherapy and surgery, and possibly radiation therapy. Traditional treatment algorithms for this pathology include the surgical stage and systemic or intracavitary chemotherapy, while the treatment sequence may be different and depends primarily on the prevalence of the disease. For solitary fibrous tumor, surgical treatment, by contrast, is the method of choice. Thus, when choosing a treatment strategy for a primary peritoneal tumor, it is first of all necessary to take into account the morphological type of the tumor and rely on known data on the benefits of a particular method. In this article, we tried to present modern information on the diagnosis and treatment of rare forms of primary peritoneal tumors.

Histopathological Classification of Canine Cutaneous Round Cell Tumors Using Deep Learning: A Multi-Center Study

Canine cutaneous round cell tumors (RCT) represent one of the routine diagnostic challenges for veterinary pathologists. Computer-aided approaches are developed to overcome these restrictions and to increase accuracy and consistency of diagnosis. These systems are also of high benefit reducing errors when a large number of cases are screened daily. In this study we describe ARCTA (Automated Round Cell Tumors Assessment), a fully automated algorithm for cutaneous RCT classification and mast cell tumors grading in canine histopathological images. ARCTA employs a deep learning strategy and was developed on 416 RCT images and 213 mast cell tumors images. In the test set, our algorithm exhibited an excellent classification performance in both RCT classification (accuracy: 91.66%) and mast cell tumors grading (accuracy: 100%). Misdiagnoses were encountered for histiocytomas in the train set and for melanomas in the test set. For mast cell tumors the reduction of a grade was observed in the train set, but not in the test set. To the best of our knowledge, the proposed model is the first fully automated algorithm in histological images specifically developed for veterinary medicine. Being very fast (average computational time 2.63 s), this algorithm paves the way for an automated and effective evaluation of canine tumors.