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Subspecialties Histology, Oncology, Cytology

Case of the Month

A 58-year-old female presented with a right breast mass.

Which of the following immunohistochemical markers is the most specific for this entity?

a. β-catenin
b. p63
c. CK7
d. ER
e. CK20

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Submitted by Emily R. McMullen, House Officer IV at the University of Michigan, Ann Arbor, Michigan, USA.

C. Histiocytic sarcoma

Histiocytic sarcoma (HS) is a rare malignant neoplasm derived from histiocytes. It is most common in the sixth decade of life, with similar incidence among males and females. Histiocytic sarcoma most commonly occurs in extranodal locations such as soft tissue, skin, and gastrointestinal tract, but can also involve lymph nodes. Histologically, the malignant cells are usually large, reminiscent of histiocytes, with mild to severe pleomorphism. Varying numbers of inflammatory cells (small lymphocytes, histiocytes, plasma cells, and eosinophils) can be seen in the background. By immunohistochemistry, HS is usually positive for multiple histiocytic markers: CD4, CD11c, CD14, CD63, CD163, lysozyme, PU.1, and CD45. A subset of cases is S100-positive; another carries the BRAF V600E mutation.

Differential diagnosis includes hematopoietic tumors (large cell lymphomas of B and T cell lineage, classic Hodgkin lymphoma, myeloid sarcoma), dendritic cell neoplasms (follicular and interdigitating dendritic cell sarcoma), Langerhans cell sarcoma, Rosai-Dorfman disease, and non-hematopoietic neoplasms. Among these, carcinoma and melanoma with histiocytic features should be excluded. A variety of mesenchymal neoplasms is also in the differential diagnosis of HS, including inflammatory myeofibroblastic tumor, liposarcoma (inflammatory or dedifferentiated), myxoinflammatory fibroblastic sarcoma, histiocytic variant of angiosarcoma, and others. A large panel of immunostains is usually needed to resolve the differential diagnosis and make a diagnosis of HS.

Although Langerhans cell sarcoma can stain positive for S100, it typically stains for CD1a and langerin, which are not seen in histiocytic sarcoma. Interdigitating dendritic cell sarcoma also stains for S100, but the staining pattern is usually much stronger and diffuse than seen in histiocytic sarcoma. Furthermore, CD68 and CD163 staining in interdigitating dendritic cell sarcoma is generally only focal, if present at all.  Unlike histiocytic sarcoma, follicular dendritic cell sarcoma will typically stain for dendritic markers such as CD21, CD23, or CD35.

Histiocytic sarcoma is an aggressive tumor with no well-established management; however, most patients are treated with the CHOP (cyclophosphamide, daunorubicin, vincristine, and prednisone) chemotherapy protocol common in lymphoma treatment. Median survival for treated patients is approximately 2.5 years. A subset of cases shows PD-L1 expression, which could have therapeutic implications for future treatment. 

Submitted by Kyle D. Perry, Senior Pathologist,  Henry Ford Health System, Detroit, MI, USA.

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  1. JL Hornick et al.,  Am J Surg Pathol, 28, 1133 (2004). PMID: 15316312.
  2. SH Swerdlow et al., WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. International Agency for Research on Cancer: 2017.
  3. F Facchetti et al.,  Virchows Arch, 471, 467 (2017). PMID: 28695297.
  4. JS Reis-Filho et al., WHO Classification of Tumours of the Breast, 4th edition. International Agency for Research on Cancer: 2012.
  5. N Cha et al., Am J Case Rep, 19, 203 (2018). PMID: 29472521.
  6. ER McMullen et al., Arch Pathol Lab Med, 143, 1492 (2019). PMID: 31765246.
  7. MM Koker, CG Kleer, Am J Surg Pathol, 28, 1506 (2004). PMID: 15489655.
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