These rare sarcomas arise from the interdigitating reticulum cells of the lymph node froming a nodal based sarcoma. They are abbreviated IDCS and are derived from cells normally found in the nonlymphoid accessory cells of the T-cell areas of the peripheral lymphoid tissue. They lack Birbeck granules and are important in antigen presentation to the T-cells. These tumors must be distinguished from the closely related follicular dendritic cell sarcoma.
IDCS generally manifests with lymphadenopathy, rarely with associated systemic symptoms including fever and weight loss. The tumors are common in the lymph nodes, intrabdominal organs such as pancreas and peripancreatic tissue, tonsils, and other extranodal sites.
The International Lymphoma Study Group has identified the following classification scheme:
CATEGORY DISEASES Macrophage/Histiocytic neoplasms Histiocytic sarcoma Dendritic Cell Neoplasms Langerhans Cell Tumor
Langerhans Cell Sarcoma
Interdigitating Cell Tumor/Sarcoma
Follicular Dendritic Cell Tumor/Sarcoma
DISEASE CD68 LYS CD1a S100 CD21 CD35 Histiocytic sarcoma + + - +/- - - Langerhans cell tumor/sarcoma + +/- + + - - Interdigitating cell tumor/sarcoma +/- - - + - - Follicular dendritic cell tumor/sarcoma +/- - - +/- + +
Adapted from Pileri SA, Grogan TM, Harris NL, etal. Histopathology 2002;31:1-29.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Reticulum cell sarcoma
Interdigitating cell sarcoma
INCIDENCE Very rare, >50 cases reported AGE RANGE-MEDIAN 8 to 77 years, with a median age of 52 years SEX (M:F) Males 1.5:1
DISEASE ASSOCIATIONS CHARACTERIZATION Castleman's disease May be preceded by a phase of FDC overgrowth/dysplasia in the interfollicular zones of the Castleman's disease Concurrent hematologic malignancies
Precursor T-lymphoblastic leukemia
Follicle center lymphoma
B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia
EBV Very rare except for a specific subtype occurring in the liver or spleen showing an inflammatory pseudotumor-like Schizophrenia Rare association Superior vena cava syndrome
CHARACTERIZATION General Mean size 7 cm VARIANTS BONE MARROW Rare LIVER/SPLEEN 1/3 of cases
Interdigitating Dendritic Cell Sarcoma of the Spleen: Report of a Case With a Review of the Literature.
Kawachi K, Nakatani Y, Inayama Y, Kawano N, Toda N, Misugi K.
Division of Anatomic and Surgical Pathology, Hospital of Yokohama City University, Yokohama City University School of Medicine (K.K., Y.N., Y.I., N.K.), Yokohama; and the Divisions of Internal Medicine (N.T.) and Laboratories (K.M.), Ashigarakami Hospital, Kanagawa Prefecture, Japan.; Dr. Kawachi is presently affiliated with the Department of Pathology, Yokohama City University Medical Center, Yokohama.
Am J Surg Pathol 2002 Apr;26(4):530-537 Abstract quote
Interdigitating dendritic cell sarcoma is an extremely rare neoplasm that mainly occurs in the lymph nodes.
We report a case of interdigitating dendritic cell sarcoma arising from the spleen, a previously unreported site for interdigitating dendritic cell sarcoma. An 87-year-old woman, visiting Ashigara Hospital with complaints of palpitation and dyspnea, was found to have pancytopenia and low proteinemia. Abdominal ultrasonography and CT scanning demonstrated severe splenomegaly with heterogeneous enhancement. She received a splenectomy under the clinical diagnosis of a splenic tumor. Grossly, the spleen was markedly enlarged, with confluent massive nodules. Microscopically, the normal architecture was effaced with diffuse proliferation of large pleomorphic cells arrayed in a somewhat sheet-like pattern. Erythrophagocytosis was commonly observed. Immunohistochemical studies showed that the tumor cells were positive for S-100 protein, fascin, vimentin, and CD68, but uniformly negative for CD45, B- and T-cell markers, CD1a, CD30, complement receptors, CD34, Factor VIII, HMB-45, and lysozyme.
Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes. Birbeck granules were absent. Based on these findings, the present case was diagnosed as interdigitating dendritic cell sarcoma. The patient died of multiple liver metastases 3 months postoperatively.
NASOPHARYNX SMALL INTESTINE
- Interdigitating dendritic cell sarcoma of the duodenum with rapidly fatal course: a case report and review of the literature.
Kanaan H, Al-Maghrabi J, Linjawi A, Al-Abbassi A, Dandan A, Haider AR.
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia.
Arch Pathol Lab Med. 2006 Feb;130(2):205-8. Abstract quote
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.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Neoplastic proliferation can range from dense, whorled spindle cells to haphazardly arranged, plump, histiocytoid cells
Diffuse proliferation of oval to spindled cells with a variety of described growth patterns, including sinusoidal, nesting, fascicular, and storiform
Partially or completely replaces the affected tissue
Collagenous or hyalinized background, with increased reticulin, may be present
Individual cells have a slender, spindled to plump (histiocytoid) appearance with ill-defined cell borders, abundant eosinophilic cytoplasm, and enlarged indented nuclei
Scattered multinucleated cells are common
Necrosis is unusual
Mitotic rate is variable, but generally moderate, with maximum reported rate of 10 per 10 high-powered fields
A characteristic feature is the presence of lymphocytes and plasma cells sprinkled throughout the neoplasm
CHARACTERIZATION Special stains Immunoperoxidase Positive: FDC markers (CD21, CD35, CD23); EMA
Positive in proportion of cases: Desmoplakin, S-100, CD68, actin
Negative: Cytokeratin, HMB-45, vascular markers
Interdigitating Dendritic Cell Sarcoma A Report of Four Cases and Review of the Literature
Erich M. Gaertner, etal.
Am J Clin Pathol 2001;115:589-597 Abstract quote
To better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included 1 case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node.
Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm.
All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally, the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months.
- A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor.
Grogg KL, Macon WR, Kurtin PJ, Nascimento AG.
1Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Mod Pathol. 2005;18:260-266 Abstract quote
Clusterin, a glycoprotein implicated in many cellular functions including apoptosis, has recently been shown to be strongly expressed in follicular dendritic cell tumors, and to be absent or only weakly expressed in other dendritic cell tumors. Fascin has also been investigated as a potential marker of dendritic cell neoplasms.
We evaluated staining for antibodies directed against these two antigens in 202 spindle cell tumors, including cases of follicular dendritic cell tumor (n=14), interdigitating dendritic cell tumor (n=7), leiomyosarcoma (n=17), inflammatory myofibroblastic tumor (n=13), inflammatory pseudotumor (n=2), spindle cell thymoma (n=17), synovial sarcoma (n=11), fibrosarcoma (n=14), liposarcoma (n=27), gastrointestinal stromal tumor (n=13), malignant fibrous histiocytoma (n=18), angiomatoid fibrous histiocytoma (n=4), angiosarcoma (n=10), malignant peripheral nerve sheath tumor (n=8), malignant melanoma (n=16), and spindle cell carcinoma (n=11). Among these spindle cell neoplasms, strong diffuse clusterin staining had an overall specificity of 93% and a sensitivity of 100% for follicular dendritic cell tumor.
Clusterin staining was least reliable in distinguishing follicular dendritic cell tumor from spindle cell thymoma or malignant fibrous histiocytoma, but these are entities that usually can be distinguished by clinical and morphologic data. Rare cases of leiomyosarcoma, fibrosarcoma and angiosarcoma may show strong clusterin staining. Fascin staining was very nonspecific among spindle cell tumors and thus does not imply a dendritic cell lineage.
Clusterin expression distinguishes follicular dendritic cell tumors from other dendritic cell neoplasms: report of a novel follicular dendritic cell marker and clinicopathologic data on 12 additional follicular dendritic cell tumors and 6 additional interdigitating dendritic cell tumors.
Grogg KL, Lae ME, Kurtin PJ, Macon WR.
Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Am J Surg Pathol. 2004 Aug;28(8):988-98. Abstract quote
While tumors of dendritic cell lineage may have overlapping histomorphologic features, most but not all cases can be classified using an immunohistochemical panel, including CD21, CD23, CD35, CD1a, and S-100.
Based on observations that clusterin is expressed in benign follicular dendritic cells, clusterin expression in 32 dendritic cell tumors was evaluated. Diffuse strong staining for clusterin was seen in 12 of 12 follicular dendritic cell tumors. Two of these cases were negative for traditional markers (CD21, CD23, CD35); they were classified based on characteristic ultrastructural features. Three of 6 interdigitating dendritic cell tumors were negative for clusterin and 3 showed focal weak positivity. Clusterin staining in Langerhans cell histiocytosis ranged from negative (6 of 14) to weak/moderate (8 of 14). Follicular dendritic cell tumors behaved as benign tumors or low-grade sarcomas. Interdigitating dendritic cell tumors demonstrated a widely variable behavior, ranging from benign to rapidly fatal disease.
Based on this initial study, strong clusterin staining supports a diagnosis of follicular dendritic cell tumor. Thus, staining for clusterin is useful in classification of dendritic cell tumors, particularly when the more common markers of follicular dendritic cells are not expressed.
ELECTRON MICROSCOPY Interwoven villous cell processes
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES FOLLICULAR DENDRITIC CELL SARCOMA Consider FDC sarcoma in the following situations Any unusual-looking neoplasm that is CK-negative
Thymoma-like tumor outside the mediastinum
Meningioma-like tumor outsied the dura
Malignant fibrous histiocytoma-like tumor
Gastrointestinal stromal tumor rich in lymphoid cells
Carcinoma showing thymus-like element (CASTLE) of the thyroid or soft tissue of neck
IP-LIKE FDC TUMOR CONVENTIONAL FDC TUMOR SEX M<<F M=F LOCATION Intraabdominal, especially liver and spleen Lymph nodes and various extranodal sites SYSTEMIC SYMPTOMS Common Uncommon HISTOLOGY Dispersed tumor cells; many plasma cell and lymphocytes More compact tumor cells; light sprinkling of lymphocytes BEHAVIOR Indolent Variable; intraabdominal ones are aggressive EBV Always present Rare <4%
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Recurrence >40% (may be delayed)
Metastasis >25% (lymph nodes, liver, lung)
Unfavorable prognostic factors:
Intraabdominal location (most significant)
Mitoses >5/10 hpf
Significant cellular atypia
Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases.
Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan JK, Favera RD, Delsol G, De Wolf-Peeters C, Falini B, Gascoyne RD, Gaulard P, Gatter KC, Isaacson PG, Jaffe ES, Kluin P, Knowles DM, Mason DY, Mori S, Muller-Hermelink HK, Piris MA, Ralfkiaer E, Stein H, Su IJ, Warnke RA, Weiss LM.
Service of Pathologic Anatomy and Hematopathology, Institute of Haematology and Clinical Oncology L.e A. Seragnoli, Bologna University, Italy.
Histopathology 2002 Jul;41(1):1-29 Abstract quote
Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein.
This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features.
The four groups then included: (i) histiocytic sarcoma (n=18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with 'malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n=26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n=17) designated LCT; and cytologically malignant (n=9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n=13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%).
These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n=4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered.
We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms.
Aggressive neoplasm, generally unresponsive to conventional therapy and leading to widespread disease
Of the 24 cases with follow-up, 9 patients died of disease and 7 were alive with persistent or progressive disease after therapy
Eight of the nine patients died within one year of diagnosis
One died at 16 months after diagnosis
Surgical excision of the mass lesion with multiagent, systemic chemotherapy. Radiation therapy, alone or with multiagent chemotherapy, was used in several cases
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