Chediak-Higashi syndrome

* Thrombocytopenia as a complication of B-cell lymphoma usually results from the removal of platelets from the circulation by splenic and hepatic mononuclear phagocytes.1-2 In the present paper, we describe a case of B-cell lymphoma with thrombocytopenia in which the platelets were phagocytosed by the patient's own neutrophilic granulocytes. This finding suggests that neutrophilic granulocytes actively participate in immune platelet clearance.

A 77-year-old white woman was diagnosed with stage IVB high-grade B-cell lymphoma in February of 1995. The lymphoma involved the bone marrow, pleura, spleen, and periaortic lymph nodes. At the time of diagnosis, her white blood count was 6 x 10^sup 9^/L with 42% segments, 1% bands, 1% metamyelocytes, 29% monocytes, 20% lymphocytes, and 7% atypical lymphocytes. The hemoglobin was 100 g/L and the hematocrit was 28.8%. The electronic count of the platelets was 65 x 10^sup 9^/L with prominent "satellitism" (Figure 1). The patient received 6 courses of chemotherapy with full doses of cyclophosphamide (1100 mg), adriamycin (75 mg), vincristine (2 mg), and prednisone (100 mg) supplemented with Neupogen and Epogen. She received a total of 65 doses of Neupogen (300 (mu)g, subcutaneously) and 12 doses of Epogen (10 000 units, subcutaneously) ; the last doses were administered on June 26, 1995 and April 24, 1995, respectively. Chemotherapy was completed on June 15, 1995.

During treatment, the white blood count varied between 0.2 and 14.3 x 10^sup 9^/L, the hemoglobin varied between 78 and 117 g/L, and the platelet count varied between 68 and 32 x 10^sup 9^/L. There was persistent prominent platelet "satellitism." Two weeks after the completion of chemotherapy the patient developed central nervous system lymphoma manifested as left third cranial nerve palsy and ptosis. Her platelet count was 10.8 x 10^sup 9^/L, with prominent "satellitism." After a course of whole brain radiation (25 Gy between July 13, 1995 and August 1, 1995), intrathecal methotrexate (15 mg on July 7, 1995), and AraC injection (100 mg on July 15, July 21, August 4, and August 15, 1995), there was clinical improvement. In August of 1995, the patient was admitted to the hospital because of extreme weakness. Her platelet count was 55 x 10^sup 9^/L with prominent "satellitism." The white blood count was 3.2 x 10^sup 9^/L with 75% neutrophils. Among these neutrophils, 44% exhibited from 1 to 4 intracytoplasmic phagocytosed platelets (Figures 2 and 4). Some neutrophils both exhibited "satellitism" and contained phagocytosed platelets (Figure 4). This neutrophilic thrombophagocytosis was first detected 8 weeks after the last doses of chemotherapeutic agents with Neupogen-Epogen supplementation and 1 week after central nervous system treatment. Monocytes and other leukocytes were not involved (Figure 3). Both "satellitism" and thrombophagocytosis were consistently noted in subsequent examinations.

COMMENT

Phagocytosis of autologous platelets by neutrophilic granulocytes was thought to be an in vitro phenomenon.3,4 Antiplatelet antibodies have been demonstrated to entice the neutrophilic granulocytes to ingest suitably opsonized platelets 4 These antibodies are also responsible for the platelet "satellitism" in which the platelets arrange themselves selectively around neutrophils to form rosettes.5 This patient had platelet "satellitism" when first seen (Figure 1). Her initial electronic platelet count was 65 x 10^sup 9^/L. The subsequent counts were between 32 and 10.8 X 10^sup 9^/ L. Platelet "satellitism" remained unchanged. When her platelet count was 55 X 10^sup 9^/L (ie, 8 weeks after chemotherapy with Neupogen-Epogen supplementation and 1 week after central nervous system treatment), 44% of neutrophilic granulocytes showed intracytoplasmic platelets (Figures 2 and 4). Unlike the large basophilic inclusions in May-Hegglins anomaly or Chediak-Higashi syndrome, and unlike the protozoa Babesia microti inside erythrocytes, the phagocytosed platelets were morphologically similar to the free and "satellitized" ones. In contrast to the rare phenomenon of superimposition of platelets on neutrophils, ultrastructurally, the phagocytosed platelets were enclosed in vacuoles (phagolysosomes) within the neutrophils.3,4 The variations in platelet counts do not appear to affect the presence of thrombophagocytosis and "satellitism." Although antiplatelet antibodies were not examined, the patient's platelet "satellitism" and neutrophilic thrombophagocytosis suggest the presence of these antibodies.

During treatment, the patient received Neupogen as a supplement. Neupogen acts as a granulocyte-colony-stimulating factor and is known to cause thrombocytopenia. Its mechanism has not been clearly defined. However, Neupogen can enhance the phagocytic activities of neutrophilic leukocytes ; including activity directed at autologous platelets. This activity would lead to a decrease in free platelets in vivo.7 Therefore, patients who have enhanced leukocyte-platelet interaction manifested by platelet "satellitism" may have spurious thrombocytopenia due to neutrophilic thrombophagocytosis.

Platelet "satellitism" is an uncommon phenomenon and neutrophilic thrombophagocytosis is rare. We report a case of high-grade B-cell lymphoma with both platelet "satellitism" and neutrophilic thrombophagocytosis. The latter phenomenon occurred after several medical treatments, including Neupogen treatment. The patient's platelets were phagocytosed by her own neutrophilic granulocytes. When Neupogen is given to patients with enhanced platelet-leukocyte interaction, the possibility of spurious neutrophil-mediated thrombocytopenia and thrombophagocytosis should be kept in mind.

We would like to thank Ginger Engeldinger, CLSp(H) MT HHS, of the Hematology Laboratory of St Joseph Regional Health Center for her initial observation of this rare and interesting phenomenon and her technical assistance.

References

1. Anderson JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994;330:1560-1564.

2. Schwartz RS. Treating chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1994;330:1609-1610.

3. Handin RI, Stossel TP. Phagocytosis of antibody-coated platelets by human granulocytes. N Engl J Med. 1974;290:989-993.

4. Sipka S, Laczko J, Szabados S, et al. Phagocytosis of autologous platelets by human neutrophilic granulocytes. Ada Morphologica Hungaria 1995;39:97-- 105.

5. Bizarro N, Goldschmeding R, Von Dom Borne A. Platelet satellitism is for RIII (CD16) receptor-mediated. Am J Clin Pathol. 1995;103:740-744.

6. Weisbart RH, Kacena A, Golde DW. GM-CSF induces human neutrophil IgA mediated phagocytosis by an IgA Fc receptor activation mechanism. Nature. 1988;352:647-648.

7. Peters M, Hyderman RS, Klein NJ. Platelet satellitism. N Engl J Med. 1998; 339:131-132.

Accepted for publication March 8, 2000.

From the Department of Pathology, St Joseph Regional Health Center, Bryan, Tex (Dr Lee) and the Cancer Clinic, Bryan, Tex (Dr Tripathy).

Reprints: J. C. Lee, MD, PhD, 2112-B Villa Maria, PO Box 3505, Bryan, TX 77805-3505.

Copyright College of American Pathologists Oct 2000
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