Case of the Month: Hematopathology

February 2017 Case of the Month authored by Hematopathology Fellow Robert P. Seifert, M.D.

Clinical history

A 26-year-old woman with a history of iron deficiency anemia presented to the emergency department with fatigue, abdominal pain and an 18-month history of significant weight loss (100 pounds). She also experienced night-sweats and had a nearly six-month history of voluminous diarrhea. The patient presented to other hospitals before coming to University of Florida Health, but a proper workup for her was deferred due to financial concerns.

Computerized tomography scans demonstrated left-retroperitoneal lymphadenopathy, in addition to bulky lymphadenopathy in the left inguinal, pelvic and external iliac chains. The largest lymph node was approximately 6.1 cm in greatest dimension.

Initial biopsies were not definitive for lymphoma. Eventually, a biopsy demonstrated scattered, large, atypical cells in a polymorphous inflammatory background (Figure 1).

Figure 1: This lymph node biopsy, shows frequent Reed-Steinberg cells with a mixed inflammatory background (H&E 200x).


Immunohistochemical studies showed the large atypical cells to be CD30(+), MUM1(+), CD15(weakly +), with a subset of the large cells showing reactivity for perforin and CD4 (Figures 2a/2b and 3).

Figures 2a and 2b: CD30 (3a) and CD15 (3b) immunohistochemical stains are positive in the Reed-Steinberg cells (200x).

Figure 2a:

Figure 2b:

Figures 3a and 3b: Perforin immunostatin highlights the Reed-Steinberg cells (3a), which are negative for PAX5 (3b) (200x).

Figure 3a:

Figure 3b:

The cells were found to be negative for CD45, PAX5, CD3, CD8, CD7, ALK1, OCT2, CD20, CD79a and Epstein-Barr virus. T-cell receptor gamma gene rearrangement assays and flow cytometry studies were found to be negative for clonal T- and B-cells, respectively.


(Hover the cursor over the link above to read the diagnosis for this case.)



Classic Hodgkin's lymphoma is defined by the presence of large, atypical Reed-Sternberg (RS) cells. These cells are typically of B-cell origin and are thought to originate from germinal center B-cells. Interestingly, cells with morphologic features resembling RS cells can be seen in the background of reactive lymphadenopathies, as well as non-Hodgkin's lymphomas. Among low-grade B-cell lymphomas, RS-like cells can be seen in chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma or marginal zone lymphoma 1 - 3.

In T-cell lymphomas, RS-like cells are characteristically seen in angioimmunoblastic T-cell lymphoma and, more rarely, in peripheral T-cell lymphoma, not otherwise specified 1 - 3.

Some classic Hodgkin's lymphomas can have RS cells that express cytotoxic T-cell markers, such as perforin, granzyme or TIA1 4 - 5.

The perforin-positive RS cells in this case bear striking immunophenotypic similarities to the RS-like cells described in some T-cell lymphomas--namely, the lack of B-cell marker expression and presence of perforin expression. In most cases, the RS cells of classic Hodgkin's lymphoma are shown to be derived from germinal center B-cells and, thus, usually show weak expression of the B-cell marker PAX5 4.

Perforin expression in RS cells has been described in few reports in literature, and it has been associated with a worse prognosis 4 - 5. In cases of cytotoxic molecule positive classic Hodgkin's lymphoma, PAX5 expression is typically diminished and CD4 expression can be present 4. The presence of RS-like cells in T-cell lymphomas and cytotoxic molecule-positive classic Hodgkin's lymphoma may have been the cause of many years of debate as to the true progenitor for RS cells.


  1. Shin SS, Ben-Ezra J, Burke JS, Sheibani K, Rappaport H. Reed-Sternberglike cells in low-grade lymphomas are transformed neoplastic cells of B-cell lineage. Am J Clin Pathol. 1993;99(6):658–662.
  2. Bayerl MG, Bentley G, Bellan C, Leoncini L, Ehmann WC, Palutke M. Lacunar and Reed-Sternberg-like cells in follicular lymphomas are clonally related to the centrocytic and centroblastic cells as demonstrated by laser capture microdissection. Am J Clin Pathol. 2004;122(6):858–864.
  3. Tsang WY, Chan JK, Sing C. The nature of Reed-Sternberg-like cells in chronic lymphocytic leukemia. Am J Clin Pathol. 1993;99(3):317–323.
  4. Asano, Naoko, et al. "Cytotoxic molecule-positive classical Hodgkin’s lymphoma: a clinicopathological comparison with cytotoxic molecule-positive peripheral T-cell lymphoma of not otherwise specified type." haematologica 96.11 (2011): 1636-1643.
  5. Venkataraman, Girish, et al. "Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival." Blood 121.10 (2013): 1795-1804.
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