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Dendritic Cell and Histiocytic Neoplasms: Biology, Diagnosis

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Dendritic Cell and Histiocytic Neoplasms: Biology, Diagnosis Immunohistochemistry remains the mainstay of diagnosing rare dendritic cell and histiocytic neoplasms. Collaborative efforts are needed to better treat patients with these rare disorders. Mushroom Biome. Photograph courtesy of Sherri Damlo. www.damloedits.com. Dendritic Cell and Histiocytic Neoplasms: Biology, Diagnosis, and Treatment Samir Dalia, MD, Haipeng Shao, MD, PhD, Elizabeth Sagatys, MD, Hernani Cualing, MD, and Lubomir Sokol, MD, PhD Background: Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma. Methods: A literature search for articles published between 1990 and 2013 was undertaken. Articles are reviewed and salient findings are systematically described. Results: Patients with dendritic cell and histiocytic neoplasms have distinct but variable clinical presentations; however, because many tumors have recently been recognized, their true incidence is uncertain. Although the clinical features can present in many organs, most occur in the lymph nodes or skin. Most cases are unifocal and solitary presentations have good prognoses with surgical resection. The role of adjuvant therapy in these disorders remains unclear. In cases with disseminated disease, prognosis is poor and data on treatment options are limited, although chemotherapy and referral to a tertiary care center should be considered. Excisional biopsy is the preferred method of specimen collection for tissue diagnosis, and immunohistochemistry is the most important diagnostic method for differentiating these disorders from other entities. Conclusions: Dendritic cell and histiocytic cell neoplasms are rare hematological disorders with variable clinical presentations and prognoses. Immunohistochemistry remains important for diagnosis. Larger pooled analyses or clinical trials are needed to better understand optimal treatment options in these rare disorders. Whenever possible, patients should be referred to a tertiary care center for disease management. From the Departments of Medical Oncology (SD), Hematopathology Submitted December 20, 2013; accepted May 1, 2014. and Laboratory Medicine (HS, ES), and Malignant Hematology (LS) at Address correspondence to Samir Dalia, MD, Mercy Clinic Oncol- the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, ogy-Hematology, 3001 McClelland Boulevard, Joplin, MO 64804. the University of South Florida Morsani College of Medicine (SD, HS), E-mail: [email protected] Tampa, Florida, and IHCFLOW (HC), Lutz, Florida. No significant relationships exist between the authors and the com- Dr Dalia is now affiliated with Mercy Clinic Oncology-Hematology, panies/organizations whose products or services may be referenced Joplin, Missouri. in this article. 290 Cancer Control October 2014, Vol. 21, No. 4 Introduction nodes or the extranodal ectopic lymphoid tissue, Dendritic and histiocytic neoplasms are rare hema- including lymphoid nodules in the bone marrow. tological malignancies that involve common immune Through the formation of immune complexes, these accessory or mesenchymal cells. These tumors are cells store and retain antigens and serve as a nidus typically placed into 2 main groups based on their for B-cell proliferation and differentiation, along with derivation from either bone marrow precursors or help from T cells.5-7 FDCs are mesenchymal in origin mesenchymal cells. Histiocytic sarcoma (HS), Lang- and similar to myofibroblasts. Although FDCs are not erhans cell histiocytosis (LCH), and interdigitating derived from bone marrow progenitors, they express dendritic cell sarcoma (IDCS) are derived from bone antigens related to bone marrow stroma. Hence, these marrow precursors, while follicular dendritic cell sar- cells typically express markers of FDC differentiation, coma (FDCS), indeterminate dendritic cell sarcoma including CD21, CD23, and CD35.8 (INDCS), fibroblastic reticular cell tumors (FRCTs), Although FDCS is mesenchymal in origin, it is and disseminated juvenile xanthogranuloma (DJX) clonally related to follicular lymphoma, possibly are histogenetically of stromal-derived dendritic cells through transdifferentiation of the follicular lympho- or mesenchymal in origin.1,2 Divergent differentiation ma clone.3 The disease has also been associated with from marrow precursors is the normal histogenesis, Castleman disease, paraneoplastic pemphigus, and although hybrid or transdifferentiation from neoplas- myasthenia gravis.9-13 FDCS may arise in lymph nodes tic lymphoid clones has also been proposed in IDCS, that harbor dysplastic FDCs in Castleman disease, with HS, or FDCS.2-4 Together, dendritic and histiocytic neo- some studies reporting clonal expansion of FDCs in plasms make up less than 1% of neoplasms presenting these patients.14,15 FDCS and non-neoplastic FDCs of in the lymph nodes or soft tissues. Castleman disease express epidermal growth factor re- The rarity of these tumors makes them difficult ceptor, which may promote FDC persistence and allow to accurately diagnose and treat, and they are often for mutations that may result in FDCS.16 In addition, mistaken as non-Hodgkin lymphoma or other lymph- a correlation exists between FDCS and the presence oproliferative disorders. Patients with suspected den- of Epstein–Barr virus (EBV).17 Because FDCs express dritic and histiocytic neoplasms require hematopathol- CD21 (acting as a receptor for EBV), the virus could ogy consultation and should be referred to a tertiary gain entry into these cells.18-20 The differential diagno- care cancer center when possible. The diagnosis of sis of FDCS remains broad and includes B- and T-cell these rare disorders is based on differential features lymphomas, myeloid sarcomas, melanoma, carcino- in morphology and immunohistochemistry. Recent mas, and other dendritic and histiocytic disorders, such advances in immunohistochemistry have helped in a as blastic plasmacytoid dendritic cell neoplasms and better classification of dendritic cell and histiocytic LCH (Table 1). Rarely, peripheral nerve sheath tumors neoplasms and have improved our knowledge of their and malignant fibrous histiocytoma are mistaken for tumor biology and histogenesis, which may be helpful FDCS; immunohistochemistry might help in the diag- in the management of these rare diseases. The aim of nosis of these entities.21,22 this review is to provide clinicians with the current scientific framework to better understand the tumor Clinical Features biology, clinical features, pathology, and treatment of FDCS presents in a wide range of ages, but it shows FDCS, IDCS, INDCS, HS, FRCT, and DJX. adult predominance (mean age, 44 years).23,24 Local- We performed a literature search for articles pub- ized FDCS has a benign course, a median survival lished between January 1, 1990, and December 1, 2013, rate of 168 months (range, 2–360 months), and risks to find research related to tumor biology, clinical fea- of local recurrence and distant metastasis of 27% to tures, pathology, and treatments for each of these rare 28%, respectively.10 Larger tumor size (≥ 6 cm), the disorders. We referred to the text and references of the presence of coagulative necrosis, high mitotic count fourth edition of the WHO Classification of Tumours (≥ 5 per 10 HPF), and cytological atypia are associated of Haematopoietic and Lymphoid Tissues1 as a basis to with a poor prognosis.8,10,25 Stage did not significantly comprehensively cover these disorders. Although LCH impact overall survival rates in patients with FDCS.10 is integral in understanding these entities, it has been Saygin et al10 reported that 2-year survival rates for separately reviewed by Dr Grana on page 328 of this early, locally advanced, and distant metastatic disease issue and will not be covered here. were 84.2%, 80%, and 42.8%, respectively. In the majority of cases, FDCS presents as a Follicular Dendritic Cell Sarcoma slow-growing mass, usually with the most frequent Tumor Biology location in the head and neck or abdominal lymph FDCS is a very rare clonal neoplasm of follicular nodes. Approximately one-half of patients will present dendritic cells (FDCs). FDCs are stromal-derived cells with a local cervical and intra-abdominal mass.10,26 normally found in the germinal centers of lymph Although rare, most extranodal involvement occurs October 2014, Vol. 21, No. 4 Cancer Control 291 Table 1. — Differential Diagnosis of Dendritic Cell Sarcomas FDCS and IDCS FRCT HS INDCS JXG Anaplastic large cell lymphoma FDCS Anaplastic large cell LCH Dermatofibroma IDCS (for FDCS) or FDCS IDCS lymphoma Pityriasis rosea Eruptive xanthomas (for IDCS) INDCS Diffuse large B-cell Scabies LCH Inflammatory pseudotumors lymphoma Palisaded T-cell lymphomas Mastocytoma Intranodal myofibroblastoma Hemophagocytic myofibroblastoma (cutaneous T-cell hyperplasia, Papular xanthoma LCH lymphohistiocytosis mycosis fungoides) Sarcoma Spitz nevus Non-Hodgkin lymphoma LCH Tuberous xanthoma Peripheral nerve sheath tumors
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