College of American Pathologists
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2009 — July Case of the Month

Updated June 22, 2009


CAP Foundation July 2009 Online Case of the Month

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An otherwise healthy 21-year-old man presented with a distended abdomen. He had an enlarged spleen with focal hypoechogenic lesions revealed by ultrasonography. Splenectomy was performed. A 28.0 x 15.0 x 4.5 cm, 2100.0 gram spleen contained numerous circumscribed nodules measuring from 0.4 to 4.3 cm in diameter.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2006, Case 20 and is a Gaucher disease.

Criteria for Diagnosis and Comments:

The diagnosis is Gaucher disease of the spleen. Gaucher disease is a rare autosomal recessive disorder and is classified as a lipid lysosomal storage disease. Glucosylceramide, a product of cell membrane breakdown, is stored in the lysosomes of cells of the reticuloendothelial system because of an error in glucosylceramide-hydrolase production.

Three phenotypic manifestations of Gaucher disease have been described. Type I is the most frequent and occurs without central nervous system (CNS) lesions. Type II is the most severe form presenting in infancy with rapidly progressive neurological signs. Type III is the rarest of the three and has more slowly progressive CNS impairment.

Macrophages filled with insoluble glycolipids (Gaucher cells) are responsible for hepatosplenomegaly, anemia, thrombocytopenia, and bone manifestations (such as osteopenia, subchondral osteonecrosis, and failure to remodel) to varying degrees. An enlarged spleen is present in 90% of patients. Splenic nodules show red pulp with numerous large storage cells. These cells have eosinophilic, and usually striated or fibrillary, cytoplasm and stain faintly with PAS.

Histiocytic sarcoma of the spleen is rare. The tumor cells in the cords and sinuses of the red pulp form multiple lobulated tumors. The medium, large, and giant cells express CD68, lysozyme, and S100 protein but are negative for B- and T-cell markers, cytokeratins, HMB-45, and CD1a. Systemic malignant histiocytosis with secondary spleen involvement occurs more frequently than a primary splenic presentation but with diffuse infiltration.

Hodgkin lymphoma affects the spleen more than any other abdominal organ, and increased splenic weight appears to be related to an increased probability of finding Hodgkin lymphoma in that location. Diagnostic Reed-Sternberg (RS) cells or their mononuclear variants may be found in a background of lymphocytes, histiocytes, eosinophils, and plasma cells. Prominent nucleoli set RS cells apart from Gaucher cells seen in this case.

Interdigitating dendritic cell sarcoma involving the spleen is extremely rare. In one of the only reported cases, the spleen was markedly enlarged with massive confluent nodules. The normal splenic architecture was effaced with large pleomorphic cells arranged in a sheet-like pattern. Erythrophagocytosis was seen frequently. The tumor cells were positive for S100 protein, fascin, vimentin, and CD68 but negative for CD45, B- and T-cell markers, CD1a, CD30, complement receptors, CD34, Factor VIII, HMB-45, and lysozyme. By electron microscopy, the tumor cells showed complex interdigitating cytoplasmic dendritic processes. No Birbeck granules were seen.

Langerhans cell histiocytosis is characterized by the proliferation of abnormal dendritic antigen-presenting histiocytes known as Langerhans cells. They can be found in a background of lymphocytes, eosinophils, and neutrophils and may occur in localized or systemic disease. Isolated cases are reported of solitary splenic involvement; however, systemic spread is more common. Microscopically, Langerhans cells have folded and grooved nuclei with inconspicuous nucleoli and stain positively for S100 protein and CD1a. Ultrastructurally, the classic Birbeck granules are seen.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) typically appears with cervical lymphadenopathy but approximately 40% of cases have extranodal disease. Histologically, this entity shows sheets of pale to slightly eosinophilic macrophages with engulfment of lymphocytes, erythrocytes, or other cellular debris within their cytoplasm. Fibrosis is more common in an extranodal location. The macrophages are reactive for CD68 and S100 protein but not for CD1a.

Supplementary Questions For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which tumor shows Birbeck granules by electron microscopy? A. Gaucher disease
B. Histiocytic sarcoma
C. Hodgkin lymphoma
D. Interdigitating dendritic cell sarcoma
E. Langerhans cell histiocytosis
F. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
2. Which tumor is characterized by an S100(+), fascin(+), vimentin(+), CD68(+) phenotype? A. Gaucher disease
B. Histiocytic sarcoma
C. Hodgkin lymphoma
D. Interdigitating dendritic cell sarcoma
E. Langerhans cell histiocytosis
F. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
3. Which tumor is characterized by cells that have fibrillary cytoplasm and stain faintly with PAS? A. Gaucher disease
B. Histiocytic sarcoma
C. Hodgkin lymphoma
D. Interdigitating dendritic cell sarcoma
E. Langerhans cell histiocytosis
F. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)


  1. Audouin J, Vercelli-Retta J, Le Tourneau A, et al. Pathol Res Pract. 2003;199:107-112.
  2. Chatelain D, Bralet M-P, Briere J, Degott C, Flejou J-F. Multiple splenic nodules revealing Gaucher's disease. Histopathol. 2002;40:203-204.
  3. Germain G. Gaucher's disease: a paradigm for interventional genetics. Clin Genet. 2004;65:77-86.
  4. Kawachi K, Nakatani Y, Ianyama Y, Kawano N, Toda N, Misugi K. Interdigitating Dendritic Cell Sarcoma of the Spleen - Report of a Case With Review of the Literature. Am J Surg Path. 2002;26:530-537
  5. Mampaey S, Warson F, Van Hedent E, De Schepper AM, Imaging findings in Langerhans' cell histiocytosis of the liver and spleen in an adult. Eur Radiol. 1999;9:96-98.
  6. Mankin HJ, Rosenthal DI, Xavier R. Gaucher Disease: New Approaches to an Ancient Disease. J Bone Joint Surg Am. 2001;83:748-763.
  7. Midorikawa Y, Kubota K, Mori M, Watanabe S, Koyama H, Kajiura N. Advanced Primary Hodgkin's Disease of the Spleen Cured by Surgical Resection: Report of a Case. Surg Today. 1999;29:367-370.
  8. Ratzinger G, Zelger B, Hobling W, Mikuz G, Zelger B. Sinus histiocytosis with massive lymphadenopathy Rosai-Dorfman: three unusual manifestations. Virchows Arch. 2003;443:797-800.
  9. Rueffer U, Sieber M, Stemberg M, et al. Spleen involvement in Hodgkin's lymphoma: assessment and risk profile. Ann Hematol. 2003;82:390-396.
  10. Siegal GP, Dehner, LP, Rosai, J. Histiocytosis X (Langerhans' cell granulomatosis) of the thymus. A clinicopathologic study of four childhood cases. Am J Surg Path. 1985;9:117-124.
J. Alan Long, MD
Fellow in Hematopathology

Gene P. Siegal, MD, PhD
Surgical Pathology Committee
University of Alabama at Birmingham
Birmingham, AL