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Test And Teach Number One Hundred and One: Part 2
Pathology (2000 ) 32, pp. 137– 138
TEST AND TEACH Number One Hundred and One: Part 2 See page 118 for case details and Figs. 1–3.
EXPLANATION AND DIAGNOSIS Our patient presented with a chronic lymphoproliferative disorder with clinical and morphological features typical of hairy cell leukemia variant (HCL-v). Morphologically the lymphoid cells contained more abundant cytoplasm and nuclear heterochromatin than is usual in hairy cell leukemia ( HCL) and a prominent nucleolus, similar to prolymphocytes, and characteristic of HCL-v. Cytoplasmic hairy projections were present and are typical of both HCL and HCL-v. The patient lacked a monocytopenia, neutropenia and had an easily aspiratable marrow with no increase in marrow reticulin, all typical in the variant form but the converse in HCL. An elevated white cell count is uncommon in HCL but frequently seen in HCL-v and often is above 50´109 /l. At presentation there are often diagnostic difficulties between HCL, HCL-v and splenic lymphoma with villous lymphocytes ( SLVL ). This usually arises because of overlapping morphological and histological features, especially if the lymphoid cells in SLVL are nucleolated. Patterns of bone marrow infiltration differ with a diffuse lymphoid infiltration in HCL invariably with spacing and a clear zone between cells, as well as trapping of nucleated red cells; reticulin fibrosis is common and frequently the aspirate results in a dry tap. In HCL-v, spacing between the cells is not seen, nor is fibrosis, while in SLVL a nodular partly paratrabecular infiltration is typical and a diffuse lymphoid infiltrate is seen only in advanced disease. Immunophenotypic features can also be overlapping; however, a scoring system by Matutes et al.1 has proven useful and is recommended in difficult cases. In 17 cases of HCL-v described by Saintani et al.2 all lacked CD25 and HC2, while four out of 10 expressed CD103. These antigens are nearly always expressed in HCL. CD11c is expressed in both HCL and HCL-v, although only weak antigen density is found in the variant form. Splenic histology is another useful diagnostic tool in these three chronic lymphoproliferative disorders. In HCL the white pulp is atrophic and red pulp diffusely infiltrated with pseudosinus formation. A similar pattern of red pulp expansion is seen in HCL-v, although Sainati et al. reported three of 17 cases showing concomitant white pulp infiltration. Both the red and white pulp show infiltration in SLVL. Cawley et al.3 first described HCL-v and the importance of its diagnosis relates to the differing biological features compared to HCL. HCL-v is intermediate in its features between HCL and prolymphocytic leukemia. Response to
treatment using splenectomy and a-interferon has been disappointing, while deoxycoformycin and chorambucil have shown benefits anecdotally. Hybrid, blastic and multilobular forms have been described.4,5 Our patient developed pure red cell aplasia ( PRCA) 6 months after diagnosis. He initially responded to corticosteroid therapy, was subsequently treated with 2-chlorodeoxyadenosine unsuccessfully and because of progressive disease required splenectomy. Pure red cell aplasia has not been previously reported to our knowledge with HCL-v, although it is well recognised in chronic lymphatic leukemia ( CLL),6 – 8 non-Hodgkin ’s lymphoma,9,10 and granular lymphocyte-proliferative disorders.11 The underlying mechanism of PRCA in CLL is thought due to a cytotoxic T-lymphocyte effect on erythroid progenitors rather than a specific serum inhibitor. T-suppressor cells ( T cells with IgG Fc receptor-positivity) increase in the course of CLL and in vitro studies have demonstrated significant suppressive effects on erythroid colony growth by T-suppressor cells, which is reversible by their removal. One can hypothesize a similar pathogenic mechanism exists for HCL-v and PRCA, although this is unproven. Patient survival with CLL and PRCA does not appear to be reduced and treatment with cyclophosphamide plus prednisolone has proven to be the most effective. Maintenance therapy is, however, important in preventing relapse of PRCA. Address for correspondenc e: D.A.W., Department of Pathology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, 3002, Victoria, Australia. E-mail: [email protected] u
References 1. Matutes E, Morilla R, Owusu-Amkomah K, et al. The immunopheno type of hairy cell leukaemia (HCL). Proposal for a scoring system to distinguish HCL from B-cell disorders with hairy or villous lymphocytes. Leuk Lymphoma 1994; 14 (Suppl 1): 57– 61. 2. Sainati L, Matutes E, Mulligan S, et al. A variant form of hairy cell leukaemia resistant to a-interferon: clinical and phenotypic characteristics of 17 patients. Blood 1990; 76: 157–62. 3. Cawley JC, Burns GF, Hayhoe FGJ. A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia. Leuk Res 1980; 4: 547– 59. 4. Sun T, Susin M, Shevde N, Teichberg S. Hybrid form of hairy cell leukaemia and chronic lymphocytic leukaemia. Hematol Oncol 1990; 8: 283– 94. 5. Diez Martin JL, Li Chin-Yang, Banks PM. Blastic variant of hairy-cell leukaemia. Am J Clin Pathol 1987; 87: 576–83. 6. Abeloff MD, Waterbury L. Pure red blood cell aplasia and chronic lymphocytic leukaemia. 1974; 134: 721–4.
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/020137 – 02 © 2000 Royal College of Pathologists of Australasia
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7. Chikkappa G, Zarrabi MH, Tsan MF. Pure red-cell aplasia in patients with chronic lymphocytic leukaemia. Medicine 1986; 65: 339– 51. 8. Christen R, Morant R, Fehr J. Cyclosporin-A therapy of pure red cell aplasia in a patient with B-cell chronic lymphocytic leukaemia. Eur J Haematol 1989; 42: 303–7. 9. Hunt FA, Lander CM. Successful use of combination chemotherapy in
Pathology ( 2000 ), 32, May pure red cell aplasia associated with malignant lymphoma, histiocytic type. Aust NZ J Med 1975; 5: 468–71. 10. Carloss HW, Saab GA, Tavossoli M. Pure red cell aplasia and lymphoma. J Am Med Assoc 1979; 67: 242– 3. 11. Yamada O, Mizoguchi H, Oshimi K. Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte-proliferativ e disorders. Br J Haematol 1997; 97: 392–9.
TEST AND TEACH Number One Hundred and One: Part 2 See page 118 for case details and Figs. 1–3.
EXPLANATION AND DIAGNOSIS Our patient presented with a chronic lymphoproliferative disorder with clinical and morphological features typical of hairy cell leukemia variant (HCL-v). Morphologically the lymphoid cells contained more abundant cytoplasm and nuclear heterochromatin than is usual in hairy cell leukemia ( HCL) and a prominent nucleolus, similar to prolymphocytes, and characteristic of HCL-v. Cytoplasmic hairy projections were present and are typical of both HCL and HCL-v. The patient lacked a monocytopenia, neutropenia and had an easily aspiratable marrow with no increase in marrow reticulin, all typical in the variant form but the converse in HCL. An elevated white cell count is uncommon in HCL but frequently seen in HCL-v and often is above 50´109 /l. At presentation there are often diagnostic difficulties between HCL, HCL-v and splenic lymphoma with villous lymphocytes ( SLVL ). This usually arises because of overlapping morphological and histological features, especially if the lymphoid cells in SLVL are nucleolated. Patterns of bone marrow infiltration differ with a diffuse lymphoid infiltration in HCL invariably with spacing and a clear zone between cells, as well as trapping of nucleated red cells; reticulin fibrosis is common and frequently the aspirate results in a dry tap. In HCL-v, spacing between the cells is not seen, nor is fibrosis, while in SLVL a nodular partly paratrabecular infiltration is typical and a diffuse lymphoid infiltrate is seen only in advanced disease. Immunophenotypic features can also be overlapping; however, a scoring system by Matutes et al.1 has proven useful and is recommended in difficult cases. In 17 cases of HCL-v described by Saintani et al.2 all lacked CD25 and HC2, while four out of 10 expressed CD103. These antigens are nearly always expressed in HCL. CD11c is expressed in both HCL and HCL-v, although only weak antigen density is found in the variant form. Splenic histology is another useful diagnostic tool in these three chronic lymphoproliferative disorders. In HCL the white pulp is atrophic and red pulp diffusely infiltrated with pseudosinus formation. A similar pattern of red pulp expansion is seen in HCL-v, although Sainati et al. reported three of 17 cases showing concomitant white pulp infiltration. Both the red and white pulp show infiltration in SLVL. Cawley et al.3 first described HCL-v and the importance of its diagnosis relates to the differing biological features compared to HCL. HCL-v is intermediate in its features between HCL and prolymphocytic leukemia. Response to
treatment using splenectomy and a-interferon has been disappointing, while deoxycoformycin and chorambucil have shown benefits anecdotally. Hybrid, blastic and multilobular forms have been described.4,5 Our patient developed pure red cell aplasia ( PRCA) 6 months after diagnosis. He initially responded to corticosteroid therapy, was subsequently treated with 2-chlorodeoxyadenosine unsuccessfully and because of progressive disease required splenectomy. Pure red cell aplasia has not been previously reported to our knowledge with HCL-v, although it is well recognised in chronic lymphatic leukemia ( CLL),6 – 8 non-Hodgkin ’s lymphoma,9,10 and granular lymphocyte-proliferative disorders.11 The underlying mechanism of PRCA in CLL is thought due to a cytotoxic T-lymphocyte effect on erythroid progenitors rather than a specific serum inhibitor. T-suppressor cells ( T cells with IgG Fc receptor-positivity) increase in the course of CLL and in vitro studies have demonstrated significant suppressive effects on erythroid colony growth by T-suppressor cells, which is reversible by their removal. One can hypothesize a similar pathogenic mechanism exists for HCL-v and PRCA, although this is unproven. Patient survival with CLL and PRCA does not appear to be reduced and treatment with cyclophosphamide plus prednisolone has proven to be the most effective. Maintenance therapy is, however, important in preventing relapse of PRCA. Address for correspondenc e: D.A.W., Department of Pathology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, 3002, Victoria, Australia. E-mail: [email protected] u
References 1. Matutes E, Morilla R, Owusu-Amkomah K, et al. The immunopheno type of hairy cell leukaemia (HCL). Proposal for a scoring system to distinguish HCL from B-cell disorders with hairy or villous lymphocytes. Leuk Lymphoma 1994; 14 (Suppl 1): 57– 61. 2. Sainati L, Matutes E, Mulligan S, et al. A variant form of hairy cell leukaemia resistant to a-interferon: clinical and phenotypic characteristics of 17 patients. Blood 1990; 76: 157–62. 3. Cawley JC, Burns GF, Hayhoe FGJ. A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia. Leuk Res 1980; 4: 547– 59. 4. Sun T, Susin M, Shevde N, Teichberg S. Hybrid form of hairy cell leukaemia and chronic lymphocytic leukaemia. Hematol Oncol 1990; 8: 283– 94. 5. Diez Martin JL, Li Chin-Yang, Banks PM. Blastic variant of hairy-cell leukaemia. Am J Clin Pathol 1987; 87: 576–83. 6. Abeloff MD, Waterbury L. Pure red blood cell aplasia and chronic lymphocytic leukaemia. 1974; 134: 721–4.
ISSN 0031–3025 printed/ISSN 1465– 3931 online/00/020137 – 02 © 2000 Royal College of Pathologists of Australasia
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7. Chikkappa G, Zarrabi MH, Tsan MF. Pure red-cell aplasia in patients with chronic lymphocytic leukaemia. Medicine 1986; 65: 339– 51. 8. Christen R, Morant R, Fehr J. Cyclosporin-A therapy of pure red cell aplasia in a patient with B-cell chronic lymphocytic leukaemia. Eur J Haematol 1989; 42: 303–7. 9. Hunt FA, Lander CM. Successful use of combination chemotherapy in
Pathology ( 2000 ), 32, May pure red cell aplasia associated with malignant lymphoma, histiocytic type. Aust NZ J Med 1975; 5: 468–71. 10. Carloss HW, Saab GA, Tavossoli M. Pure red cell aplasia and lymphoma. J Am Med Assoc 1979; 67: 242– 3. 11. Yamada O, Mizoguchi H, Oshimi K. Cyclophosphamide therapy for pure red cell aplasia associated with granular lymphocyte-proliferativ e disorders. Br J Haematol 1997; 97: 392–9.