January 2010
Written by Mary Wren, M.D., PGY-4 Resident, Department of Pathology and Laboratory Medicine, Medical University of South Carolina.

Diagnosis
Interdigitating dendritic cell sarcoma, low-grade, involving parotid region lymph node.

Submitting Physician
Edgar Hartle, M.D., Lake Norman Regional Medical Center, Mooresville, NC.

Case History
The patient is a 59 year-old female who presents with a nodular mass in the area of her right parotid gland.

Microscopy
Conventionally stained slides reveal a lymph node with focally intact capsular and sinus elements. While some small spared areas contain reactive follicles, the majority of the nodal architecture is effaced (see Figure 1).

The diffuse, complex lesion is composed of neoplastic spindling cells in a vaguely whorled, storiform pattern with an interspersed reticular fiber network. On higher power, these neoplastic cells contain delicate, vesicular round to lobulated nuclei with varying atypia. Nucleoli range from small and multiple to single and prominent. The abundant cytoplasm is pale gray with indistinct borders. Background small lymphocytes, histiocytes, plasma cells, eosinophils, and occasional mast cells are intimately admixed with the lesion (see Figure 2).

Ancillary Studies
To determine the nature of this spindle cell malignancy, multiple rounds of paraffin section immunostains are performed. While strongly positive for vimentin, the spindle cells are negative for cytokeratin, desmin, smooth muscle actin, and ALK-1 protein. S-100 protein is diffusely moderately strong, bringing out a reticulum or network of positive cells with dendritic processes, while HMB-45 and MART-1 are negative (see Figure 3).

CD35 is negative in the neoplastic cells while highlighting the residual follicles. In the neoplastic cells, CD1a is predominantly negative with variable staining in some cells and CD68 is faintly positive (see Figure 4).
Ki-67 demonstrates moderate proliferative activity (see Figure 5).

Discussion
Interdigitating dendritic cells (IDCs) originate in the bone marrow from CD34+ precursor cells and take up residence in the T-cell region of lymphoid tissues, including the paracortex of lymph nodes and tonsils, the splenic periarteriolar lymphoid sheaths, and the thymic medulla. IDCs, along with histiocytes and follicular dendritic cells (FDCs), make up the major antigen-processing and antigen-presenting cells of the lymph nodes. IDCs specifically present antigens to T lymphocytes via a major histocompatibility complex. These cells normally have eosinophilic cytoplasm with thin, folded nuclear membranes and nuclear grooves. While they morphologically resemble Langerhans cells, IDCs are CD1a negative and lack Birbeck granules in electron microscopy. Instead, ultrastructurally, they demonstrate large interdigitating cytoplasmic processes.

Interdigitating dendritic cell neoplasms are extremely rare. Approximately 40 cases have been reported, with the largest single series consisting of four, presented in a mutli-institutional study (1). The majority occur in lymph nodes, especially cervical, while extranodal sites include the nasopharynx, tonsil, salivary gland, skin, liver, spleen, GI tract, bladder, and testis. The bone marrow is involved in 20% of cases. Those affected range in age from 2 to 86 years old with a median age of 65 years. There is only a slight male predominance of 1.16:1. Patients present with a slow growing mass and are generally asymptomatic, though B-type symptoms do occur in approximately 20%. Grossly, the lesion is lobulated with a solid cut surface. Microscopically, nodal lesions appear to arise in the paracortical region, partially or completely effacing the normal architecture. The cells are spindled or epithelioid and are arranged in sheets and a mixture of whorled, storiform, and nested patterns. There is abundant eosinophilic cytoplasm and elongated or oval nuclei with irregular or folded contours. Nucleoli may be inconspicuous or prominent. There is variable cytologic atypia and mitoses are frequent. Background inflammation includes small lymphocytes (mainly T cells), plasma cells, and eosinophils while reticulin fibers surround groups of neoplastic cells.

This complex lesion raises a broad differential diagnosis. A spindle cell neoplasm with a prominent inflammatory component requires consideration of inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT). IMT is ruled out by the negative stain for ALK-1 protein while the degree of atypia and the S100 protein expression rules out IPT (2). The negative HMB-45 and Mart-1 rule against malignant melanoma while other metastatic lesions are less likely due to the negatives stains for cytokeratin, desmin, and smooth muscle actin. The negative CD30 confirms that it is not a sarcomatous anaplastic large cell lymphoma or a fibroblastic variant of Hodgkins lymphoma.

Based on the findings of a multi-institutional review of histiocytic and accessory dendritic cell tumors, the results and patterns of staining for S100 protein, CD1a, CD35, and CD68 help classify this lesion within these related neoplasms (1). The diffusely moderate S100 protein pattern rules out histiocytic sarcoma while the predominately negative CD1a with variable weak staining makes a Langerhans cell sarcoma unlikely. The negative CD35 rules out follicular dendritic cell sarcoma and the faint CD68 staining lends additional support in best categorizing the lesion as an IDCS. Please refer to previous Cases of the Month: March 2006 – Follicular Dendritic Cell Sarcoma and December 2007 – Histiocytic Sarcoma.

IDCS has a variable clinical course with some patients alive without disease following surgical resection and radiotherapy and others dead of disease with widespread metastases within months of diagnosis (3). There is no standardization of treatment and prognostic factors have not been well defined due to the rarity of cases. There have been a few cases reported in association with various lymphoid neoplasms, including a recent account of a chronic lymphocytic leukemia/small lymphocytic lymphoma transdifferentiating into an IDCS (4).

References

1. Pileri SA, Grogan TM, Harris NL, Banks P, Campo E, Chan JK, et al.
   Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology. 2002; 41: 1-29.
   
   
2. Kutok JL, Pinkus GS, Dorfman DM, and Fletcher, CDM.
   Inflammatory pseudotumor of lymph node and spleen: an entity biologically distinct from inflammatory myofibroblastic tumor.
   Human Pathology. 2001; 32: 1382-1387.
   
   
3. Kawachi K, Nakatani Y, Inayama Y, Kawano N, Toda N, and Misugi K.
   Interdigitating dendritic cell sarcoma of the spleen: report of a case with a review of the literature.
   American Journal of Surgical Pathology. 2002: 26(4): 530-537.
   
   
4. Fraser CR, Wang W, Gomez M, Zhang T, Mathew S, Furman RR, et al.
   Transformation of chronic lymphocytic leukemia/small lymphocytic lymphoma to interdigitating dendritic cell sarcoma: evidence of transdifferentiation of the lymphoma clone.
   American Journal of Clinical Pathology. 2009; 132: 928-939.
   
   
5. Ioachim H and Medeiros LJ.
   Interdigitating dendritic cell sarcoma. Pp. 535-537, in Ioachim's Lymph Node Pathology. 4th ed. Baltimore, Ioachim H, Medeiros LJ, eds., Lippincott Williams & Wilkins, 2009.
   
   
6. Steven H. Swerdlow, Elias Campo, Nancy Lee Harris, Elaine S. Jaffe, Stefano A Pileri.
   WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. World Health Organization. 4th ed. Geneva:WHO Press;361-362.

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