Interdigitating Dendritic Cell Research Articles

Interdigitating Dendritic Cell Sarcoma Following Adult Liver Transplantation: Case Report and Literature Review

Interdigitating dendritic cell sarcoma is an extremely rare neoplasm derived from professional antigen presenting cells. We report an unusual case of such a tumor occurring in a 61-year-old woman who had undergone orthotopic liver transplantation for stage IVA2 primary hepatocellular carcinoma with a raised preoperative α-fetoprotein level, followed by tacrolimus-based immunosuppressive therapy. During her subsequent management, the tacrolimus blood levels ranged from 7.9 ng/mL to 16.1 ng/mL. Physical examination revealed bilateral neck and left axillary lymphadenopathy. No evidence of either chronic hepatitis B virus or Epstein-Barr virus could be detected in serum. An excisional biopsy of a right neck lymph node was performed. Microscopically, the normal architecture was diffusely effaced by a proliferation of spindled to ovoid cells arrayed in a fascicular, ill-defined whorled pattern and small lymphocytes were admixed in varying numbers with the tumor cells. Immunohistochemical studies showed that the tumor cells were positive for S100 protein, vimentin and CD68. Based on these findings, the case was diagnosed as an interdigitating dendritic cell sarcoma. The patient unfortunately had no response to 2 cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), and died of wide spread disease 6 months after the original biopsy. We propose that tacrolimus-based immunosuppression was associated with the development of interdigitating dendritic cell sarcoma after liver transplantation in this case.

BCL2 Chromosomal Translocation Is Not a General Feature of the Interdigitating Dendritic Cell Sarcoma

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasia of interdigitating dendritic cells. Two single case reports documenting IDCS harboring t(14;18) translocation involving immunoglobulin heavy chain (IGH) and BCL2 have been reported recently; however, one of the 2 IDCS has a synchronous follicular lymphoma, the absence or presence of a follicular lymphoma in the remaining case is not mentioned. In this study, by using polymerase chain reaction and fluorescence in situ hybridization techniques, we have showed that there is neither t(14;18)/IGH-BCL2 nor IGH gene rearrangement in 4 de novo IDCS without a concurrent or known history of a B-cell lymphoma, including follicular lymphoma, indicating that BCL2 chromosomal translocation is not a general feature of de novo IDCS.

Interdigitating dendritic cell sarcoma of the tonsil

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from antigen-presenting cells, with 55 cases reported thus far. A standard treatment modality is still being debated. This report describes a 56-year-old female who presented with right tonsillar enlargement and right submandibular swelling for 6 months. Treatment with empiric antibiotics did not result in improvement of her symptoms. Fine needle aspiration of the tonsil revealed no malignant cells. Tonsillectomy was eventually performed due to persistent symptoms. Based on microscopic findings, immunohistochemical stains, and review of the literature, the present case was finally diagnosed as IDCS of the tonsil with cervical lymph node involvement. The patient received four cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, and a clinically complete response was achieved followed by adjuvant radiation.

The phosphatidylserine receptors, T cell immunoglobulin mucin proteins 3 and 4, are markers of histiocytic sarcoma and other histiocytic and dendritic cell neoplasms

The T cell immunoglobulin mucin (TIM) proteins are a family of cell surface phosphatidyserine receptors that are important for the recognition and phagocytosis of apoptotic cells. Because TIM-4 is expressed by macrophages and dendritic cells in human tissue, we examined its expression in a range of histiocytic and dendritic cell neoplasms and found moderate to strong immunohistochemical staining in cases of juvenile xanthogranuloma and histiocytic sarcoma, and lower level staining in interdigitating dendritic cell sarcoma, Langerhans cell histiocytosis, acute monocytic leukemia (leukemia cutis), and blastic plasmacytoid dendritic cell neoplasm (hematodermic tumor). TIM-3 was first described on activated T(H)1 cells but was recently shown to also be a phosphatidylserine receptor and mediate phagocytosis. We found TIM-3 was expressed by peritoneal macrophages, monocytes and splenic dendritic cells. We found that it, like TIM-4, is expressed in a range of histiocytic and dendritic cell neoplasms, typically with strong immunohistochemical staining. Cases of diffuse large B cell lymphoma, anaplastic large cell lymphoma, metastatic malignant melanoma, and metastatic poorly differentiated carcinoma generally exhibited negative to minimal heterogenous staining for TIM-4 and TIM-3. We conclude that histiocytic and dendritic cell neoplasms consistently express TIM-3 and TIM-4 and that these molecules are new markers of neoplasms derived from histiocytic and dendritic cells.

Interdigitating dendritic cell sarcoma of the ileum recurred in multiple lymph nodes and duodenum three years after operation without chemotherapy

Neoplasms derived from interdigitating dendritic cell are extremely rare. Here we describe a case of a 47-year-old man with interdigitating dendritic cell sarcoma (IDCS) in the ileum. He was admitted to a hospital due to ileus. The ileal tumor, measuring 2 cm, was detected and resected with regional lymphadenectomy. At that time, a pathologic diagnosis of malignant peripheral nerve sheath tumor was made. The patient, who was not treated with chemotherapy, showed no signs of recurrence. After three years, we detected cervical lymphadenopathy and multiple duodenal masses in the patient in our hospital. Oval to spindle-shaped atypical cells, which resembled ileal tumor cells, infiltrated into the lymph node and duodenum. Immunohistochemical staining of these three lesions revealed positivity of S100 protein and several macrophage-related antigens. Based on the histologic and immunohistochemical analysis, the histopathologic diagnosis of IDCS was confirmed. To our knowledge, five cases of IDCS arising in the intestinal tract have been reported to date, and only one case, treated with both surgery and chemotherapy, led to remission. This is the first case that has a comparatively favorable prognosis without chemotherapy after surgery.

Histiocytic sarcoma with interdigitating dendritic cell differentiation: A case report with fine needle aspiration cytology and review of literature

A hybrid histiocytic sarcoma-interdigitating dendritic cell sarcoma was found in a small perinephric lymph node of an asymptomatic 80-year-old man, who presented a year ago with two small foci of lung metastasis found during routine chest X-ray. Fine needle aspiration cytology demonstrated interconnecting long and thin cell processes radiating from dendrite-like neoplastic cells with oval, enlongated, reniform, and irregular nuclei with vesicular chromatin and distinct nucleoli. Histology showed spindled epitheliod and histiocytic cells with abundant, slightly eosinophilic cytoplasm with indistinct cell borders and forming fascicles in a vague storiform pattern with interspersed T-lymphocytes. Immunohistochemically, the neoplastic cells were strongly positive for histiocytic markers: CD163, CD68, lysozyme, and PU.1, as well as strongly positive for dendritic cell markers: S100 and fascin, but were negative for CD1a (Langerhans cell marker), CD21/CD35 (follicular dendritic cell markers), B-cell, and T cell markers. This case is compared to the four hybrid histiocytic-dendritic sarcomas reported since 1983.

Primary nasopharyngeal interdigitating dendritic cell tumor presentation and response to radiation therapy

We report the case of a primary nasopharyngeal interdigitating dendritic cell tumor (IDDCT). A 25-year old male presented with bilateral decreased hearing, double vision, and ataxia. Flexible nasopharyngoscopy reviewed a large mass obstructing and filling the entire nasopharynx. MRI and PET-CT confirmed the presence of the primary tumor and demonstrated bilateral cervical lymphadenopathy. Biopsy of the nasopharynx revealed a hematolymphoid neoplasm with dendritic cell differentiation, most consistent with an IDDCT. The lesion was unresectable. The patient was treated with definitive radiotherapy to 66 Gy to the primary tumor and 50 Gy to the bilateral cervical lymphatics using an IMRT technique. A complete response was achieved and the patient remains disease free at the primary site 23 months after completion of radiotherapy.

Characteristics of the minor salivary gland infiltrates in Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune exocrinopathy associated with variable degree of lymphocytic infiltration of the affected organs (primarily salivary and lacrimal glands) and broad clinical manifestations. Minor salivary gland (MSG) lesions mainly consist of T and B cells, while antigen-presenting cells have been reported in heavy infiltrates. Evidence suggests that the infiltrate composition differs according to lesion severity; however, these differences are not well-defined. To investigate the differential distribution of the major infiltrating mononuclear cell (MNC) types in SS-lesions of variable severity, total-T, CD4 +-T, CD8 +-T, Treg, and B cell, macrophage (MΦ), interdigitating (iDC) and follicular dendritic cell (fDC), and natural-killer (NK)-cell incidence (%-total infiltrating MNC) was analyzed in MSG biopsies with mild ( n = 11), intermediate ( n = 13) or severe ( n = 15) lesions. T cells, CD4 +-T cells and Tregs, B lymphocytes, MΦs and iDCs were significantly different among MSG tissues with mild, intermediate or severe inflammatory lesions, while CD8 +-T cell, fDC and NK cell incidence was not correlated with lesion severity. T cell, CD4 +-T cell, T/B cell ratio and iDC incidence was negatively, whereas B cell and MΦ incidence was positively correlated with infiltration grade and biopsy focus score. Tregs predominated in intermediate lesions. Multivariate analysis revealed several associations between the incidence of each infiltrating MNC-type and disease manifestations, implying an involvement of local immune responses in systemic disease features. Our findings support that the distribution of infiltrating MNCs at the SS-lesions varies according to lesion severity and correlates with disease manifestations. The significance of this differential distribution and the underlying aetiopathogenic factors need to be elucidated.

Commentary on the WHO 2008 classification of neoplasms arising from histiocytic and other accessory cells

Histiocytes and dendritic cells belong to a group of immunoregulatory cells that are responsible for antigen processing and presentation to lymphocytes. Neoplasms of histiocytic and dendritic origin are very rare [1], making up less than 1% of tumours in lymph nodes. Thus, information regarding epidemiology, prognosis and treatment [2, 3] is scarce. Table 1 summatizes the neoplasms derived from histiocytes and other accessory cells according to the 2001 and 2008 WHO classification. Table 1 A summary of the neoplasms derived from histiocytes and other accessory cells in the 2001 and 2008 WHO classification A new entity that has been added to the 2008 WHO classification of histiocytic dendritic cell neoplasms is disseminated juvenile xanthogranuloma (JXG). JXG is a benign proliferation of histiocytes similar to those that occur in the dermis. The disease that occurs in adults with bone and lung involvement is referred to as Erdheim–Chester disease. Although most JXG are benign, activation of macrophages can lead to cytopenias, liver damage and death. Neoplastic cells are composed of small and oval to spindled histiocytes with bland nuclear features without nuclear grooves. Dermal lesions tend to have foamy (xanthomatous) cytoplasm with Touton-type giant cells. Similar to macrophages, the tumour cells express CD14, CD68 and fascin. CD1a is negative and S100 is positive in less than 20% of the cases. Some are clonal but no cytogenetic or molecular changes have been identified. An association with neurofibromatosis type 1 has been made. Although the neoplastic cells are thought to be derived from dendritic cells, they were previously classified as soft tissue tumours. The recognition of their origin from dermal/interstitial dendritic cells and association with other hematologic malignancies such as juvenile myelomonocytic leukaemia and Langerhans cell disease warranted their classification within the category of histiocytic and dendritic cell neoplasms. It is unclear whether the solitary forms of JXG should be considered a benign counterpart of disseminated JXG. In addition, the range of cytologic atypia that is exhibited by these tumours is also unknown. In the 2008 WHO classification, interdigitating dendritic cell sarcoma/tumours are to be designated interdigitating dendritic cell sarcoma, and follicular dendritic cell sarcoma/tumours are to be designated follicular dendritic cell sarcomas to better reflect their malignant potential. In contrast to the 2001 WHO classification, the 2008 WHO classification recognises two additional subtypes of rare dendritic cell tumours. These are encompassed by the term “other rare dendritic cell tumours” and include those that are myeloid-derived dendritic cells such as indeterminate dendritic cell tumour and those that are derived from stroma-derived dendritic cells such as fibroblastic reticular cell tumour. These replace the generic category of dendritic cell sarcoma, not otherwise specified. In addition, those that remain unclassifiable despite extensive workup or show hybrid features should be designated “dendritic cell tumour”, not otherwise specified. What remains unclear is the absence of criteria or terminology to recognise the spectrum of malignant potential for follicular dendritic cell sarcomas and interdigitating dendritic cell sarcomas. In summary, this group of neoplasms remains a diagnostic and clinical challenge. Due to the lack of phenotypic markers that are unique for most of the subtypes of tumours in this category, extensive panel of immunohistochemical stains in addition to molecular analyses are required. Furthermore, there are no useful stains or molecular studies to distinguish the neoplasms from reactive counterparts.

Interdigitating Dendritic Cell Tumor of the Lymph Node in the Right Submaxillary Region: A Case Report and Review of the Literature

Interdigitating dendritic cell tumor/sarcoma is an extremely rare neoplasm that mainly occurs in the lymph node, with only 51 cases reported in the literature to date. The authors report the case of a 41-year-old woman who presented with a 4-month history of a gradually enlarging painless mobile lymphadenopathy in the right submaxillary region. The lymph node mass was completely resected and was treated with 1 cycle of CHOP chemotherapy. After 10 months, she was alive with no evidence of disease. Because interdigitating dendritic cell sarcomas are rare and can show morphologic and immunohistochemical heterogeneity, correct diagnosis requires a high index of suspicion and complete pathological study.

Dendritic cell sarcomas/tumours of the breast: report of two cases

Extranodal follicular dendritic cell sarcoma/tumours (FDCS/Ts) and interdigitating dendritic cell sarcoma/tumours (IDCS/Ts) are rare neoplasms. We present two cases of FDCS/T and IDCS/T of the breast. The FDCS/T case (case 1) presented in a 31-year-old woman and the IDCS/T case (case 2) in a 67-year-old woman who both showed a firm lump in the left breast. The FDCS/T lesion superficially appeared as an anaplastic carcinoma and the IDCS/T was reminiscent of a spindle cell sarcomatoid carcinoma. Nevertheless both lesions were negative for keratins while case 1 displayed neoplastic cells strongly positive for CD21, vimentin and focally for CD68 and S-100 protein. The tumour cells of case 2 were positive for S-100, CD68 and CD45. In breast, an unusual keratin negative tumour composed predominantly of spindle cells arranged in fascicles, storiform pattern or whorls with a lymphoid rich stroma should raise suspicion for FDCS/Ts or IDCS/Ts. The distinction from malignant tumours with similar features is discussed.

Metastatic Interdigitating Dendritic Cell Sarcoma Masquerading as a Skin Primary Tumor: A Case Report and Review of the Literature

We report an unusual case of a lymph node interdigitating dendritic cell sarcoma (IDCS), metastatic to skin, in a 73-year-old patient. The patient initially presented as having a primary skin tumor with lymph node metastasis. The metastatic IDCS was initially read as an atypical fibroxanthoma. However, the morphology seen on the lymph node excision, paired with immunohistochemistry and electron microscopy studies, was diagnostic for an IDCS. Additional immunohistochemistry was performed on the shave biopsy, confirming that the skin tumor was a metastasis. IDCS is a rare tumor that belongs to the histiocytic and dendritic cell group of tumors. Diagnosing this entity is difficult without the aid of ancillary testing such as immunohistochemistry and electron microscopy. In the workup of a spindle cell neoplasm, IDCS should be included in the differential diagnosis.

Interdigitating dendritic cell sarcoma of the parotid gland: case report and literature review

Interdigitating dendritic cell sarcoma (IDCS) is an exceedingly rare neoplasm arising from the antigen-presenting cells of the immune system. We report a case of IDCS occurring in a 69-year-old man who presented to an outside institution with a painless mass in his right parotid gland for several months. He presented to our institution after undergoing a superficial parotidectomy. A diagnosis of undifferentiated neoplasm, favoring poorly differentiated carcinoma, was made at that time. He underwent a total parotidectomy and neck dissection at our institution. Microscopically, the tumor was composed of atypical spindle cells involving the parotid gland and an ipsilateral level III lymph node. Immunophenotypic analysis demonstrated positive staining for S100, fascin, vimentin, and HLA-II. Follicular dendritic cell, lymphoid, epithelial, myoepithelial, and melanoma markers were negative. Taken together, the above features were consistent with IDCS. An IDCS of the parotid gland is extremely rare, with only 2 cases reported in the literature. The unusual location and morphological similarity to follicular dendritic sarcoma and other types of soft tissue sarcomas can be a diagnostic challenge. Awareness of this tumor and the use of appropriate markers are crucial in making the diagnosis. The patient did well postoperatively, and he underwent a complete course of postoperative irradiation to the right parotid and neck.

Interdigitating dendritic cell sarcoma/tumor: a study of 3 cases

To study the pathologic features, diagnosis and differential diagnosis of interdigitating dendritic cell sarcoma (IDCS). The clinical findings, morphologic features and immunophenotype of 3 cases of IDCS were investigated. Gross examination showed that IDCS had a greyish-white to greyish-yellow cut surface. The site of occurrence included lung, spleen (with lymph node metastasis) and lymph node. Histologically, the tumor cells were arranged in nests, fascicles and whorls, with intimate admixture of many lymphocytes and plasma cells. They were oval to spindle in shape and contained pale eosinophilic cytoplasm, oval and sometimes grooved nuclei, small distinct nucleoli and ill-defined cell borders. Immunohistochemical study showed that the tumor cells expressed S-100 protein. IDCS is a rare type of histiocytic and dendritic cell malignancy with distinctive morphologic findings. It needs to be distinguished from follicular dendritic cell sarcoma, inflammatory pseudotumor, Langerhans' cell histiocytosis, malignant melanoma, undifferentiated carcinoma and anaplastic large cell lymphoma. Immunohistochemical staining for S-100 protein is helpful in confirming the diagnosis.

Primary Intratesticular Spindle Cell Tumors: Interdigitating Dendritic Cell Tumor and Inflammatory Myofibroblastic Tumor

Spindle cell neoplasms arising in the testis are uncommon; most cases belong to the category of gonadal stromal tumors, and the presence of distinctive clinical and pathological features usually lead to a definitive diagnosis. In some instances, however, the diagnosis of these tumors can be challenging and special techniques are needed. The present study reports 2 unusual cases of primary intratesticular tumors showing a striking morphology, characterized by spindle to stellate cells in a lymphoid background. The diagnosis of interdigitating dendritic cell tumor and inflammatory myofibroblastic tumor was established in the 2 cases, and their probable origin in cells of the accessory immune system is discussed. Although both tumors share similar histological features, their immunohistochemical profiles were decisive for a definitive diagnosis.

Sarcoma of follicular dendritic cells with features of sinus lining cells—a new subtype of reticulum cell sarcoma?

Dendritic cell neoplasms of the World Health Organization classification comprise Langerhans cell histiocytosis, Langerhans cell sarcoma, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, and dendritic cell sarcoma, not otherwise specified. Several studies based on immunohistochemical and ultrastructural analysis tried to further clarify the origin of these neoplasms which are thought to derive from mesenchymal or bone marrow precursors. Lymphatic vessel endothelium hyaluronan receptor-1 (LYVE-1) was recently described as a marker for lymphatic endothelium which is expressed on normal liver blood sinusoid lining cells, spleen endothelium, activated tissue macrophages, blood vessels in the lung, endothelial cells of lymphatic sinuses, and in fibroblastic reticular cells in lymph nodes. We present a case of LYVE-1-positive reticulum cell neoplasm in an axillary lymph node. To the best of our knowledge, there has been no report about LYVE-1 expression in histiocytic or dendritic cell neoplasms so far. Due to the assumed specificity of this antibody, we propose designation of this reticulum cell sarcoma as lymphatic sinus lining cell sarcoma which might finally represent another subtype of reticulum cell sarcomas.

Podoplanin (D2-40) Is a Novel Marker for Follicular Dendritic Cell Tumors

Podoplanin, recognized by monoclonal antibody D2-40, may be a useful marker for follicular dendritic cell (FDC) tumors. Paraffin sections of 125 dendritic cell, histiocytic, and spindle cell lesions were studied, including 11 FDC tumors, 5 interdigitating dendritic cell tumors, 10 histiocytic sarcomas, 5 Langerhans cell histiocytosis, 5 sinus histiocytosis with massive lymphadenopathy, 5 inflammatory pseudotumors of lymph node or spleen, 9 nodal Kaposi sarcomas, 6 inflammatory myofibroblastic tumors (IMTs), 29 gastrointestinal stromal tumors (GISTs), and 10 cases each of malignant peripheral nerve sheath tumor, leiomyosarcoma, monophasic synovial sarcoma (SS), and solitary fibrous tumor. All FDC tumors and Kaposi sarcomas showed strong immunoreactivity for podoplanin (predominantly membranous). Podoplanin expression was only occasionally observed in the other tumor types, including 7 GISTs (24%), 2 IMTs (33%), and 3 SS (30%), and was generally weak and cytoplasmic. Reactivity for podoplanin was more common in spindle cell GISTs (5/13 [38%]) than in epithelioid or mixed-type GISTs (2/16 [13%]). Podoplanin is a highly sensitive marker for FDC tumors and may be useful to help confirm the diagnosis in conjunction with conventional FDC markers, particularly in the differential diagnosis of dendritic cell and histiocytic lesions.

Interdigitating Dendritic Cell Sarcoma of Cervical Lymph Nodes

Interdigitating dendritic cell sarcoma (IDCS) is a malignant neoplasm that arises from the interdigitating reticular cells of the lymph node. Dendritic cells are a heterogeneous group of antigen-presenting cells that play a major role in innate and adaptive immune responses. Subtypes of dendritic cells include Langerhans cells, interdigitating dendritic cells, follicular dendritic cells, and dermal dendrocytes. 1 Interdigitating dendritic cells reside in the T-cell areas of peripheral lymphoid tissue, including the paracortex of lymph node and tonsil, the splenic peri-arteriolar lymphoid sheaths, and the interfollicular areas of mucosa-associated lymphoid tissue, and are responsible for major histocompatibility complex-restricted stimulation of resting T cells. Interdigitating dendritic cell sarcoma is rare; to our knowledge, only 34 cases have been reported to date. 1-4 Lymphadenopathy is the most common physical finding at presentation, and 42% of cases occur in the head and neck. 1,2,4 Otolaryngologists evaluating a head and neck mass should therefore include IDCS in the differential diagnosis.

Synchronous Interdigitating Dendritic Cell Sarcoma and B-Cell Small Lymphocytic Lymphoma in a Lymph Node

A gradually enlarging axillary mass in a 79-year-old man was excised. The specimen was processed for light microscopy, immunohistochemical studies, and electron microscopy; gene rearrangement studies were also performed. A diagnosis of an interdigitating dendritic cell tumor of the lymph node and a B-cell small lymphocytic lymphoma occurring in the same anatomic location was made. We found that although rare cases of interdigitating dendritic cell tumor with an associated secondary malignancy have been described in the literature, to our knowledge, this is the first report of interdigitating dendritic cell tumor and synchronous neoplasm diagnosed at the same site. A possible relationship between the 2 disorders is also discussed.

Interdigitating Dendritic Cell Sarcoma of the Duodenum With Rapidly Fatal Course: A Case Report and Review of the Literature

Interdigitating dendritic cell sarcoma is an extremely rare malignancy derived from antigen-presenting cells. Dendritic cells constitute a heterogeneous group of cells, which includes Langerhans cells, dermal dendrocytes, follicular dendritic cells, and interdigitating dendritic cells present in lymphoid and nonlymphoid organs. We report the case of a 36-year-old woman who presented with epigastric pain, projectile vomiting, and significant weight loss. Upper gastrointestinal endoscopy showed a duodenal lesion; a biopsy of the lesion was taken and was diagnosed as sarcoma. She underwent a Whipple procedure. A final diagnosis of interdigitating dendritic cell sarcoma was made, with liver and peripancreatic lymph node involvement. The patient deteriorated rapidly and died 4 months later. Although interdigitating dendritic cell sarcoma of the duodenum is extremely rare, we think it should be included in the differential diagnosis of unusual spindle cell tumors with a rich lymphocytic infiltrate.