Skip to main content

Hematologic Neoplasms and Selected Tumor-Like Lesions Involving the Female Reproductive Organs

  • Reference work entry
Blaustein’s Pathology of the Female Genital Tract
  • 3926 Accesses

Abstract

A variety of hematologic neoplasms involves the female reproductive organs, including a number of different types of lymphomas and lymphoid leukemias, myeloid sarcomas and myeloid leukemias, and rare histiocytic neoplasms. When the female reproductive organs are affected by one of these disorders in the setting of widespread disease, the diagnosis is usually straightforward, but in the uncommon instance in which the female genital tract is the presenting site of a hematologic neoplasm, diagnosis may be problematic, and special problems in differential diagnosis may arise.

From the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital and the Department of Pathology, Harvard Medical School, Boston, MA

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  1. Alvarez A, Ortiz J, Sacristan F (1997) Large B-cell lymphoma of the uterine corpus: case report with immunohistochemical and molecular study. Gynecol Oncol 65:534–538

    Article  PubMed  CAS  Google Scholar 

  2. Axiotis C, Merino M, Duray P (1991) Langerhans cell histiocytosis of the female genital tract. Cancer 67:1650–1660

    Article  PubMed  CAS  Google Scholar 

  3. Barcos M, Lane W, Gomez GA et al (1987) An autopsy study of 1206 acute and chronic leukemias (1958–1982). Cancer 60:827–837

    Article  PubMed  CAS  Google Scholar 

  4. Brunning R, Matutes E, Flandrin G et al (2001) Acute myeloid leukemia not otherwise categorised. In: Jaffe E et al (eds) Pathology and genetics: tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 91–105

    Google Scholar 

  5. Carbone A, Gloghini A, Libra M et al (2006) A spindle cell variant of diffuse large B-cell lymphoma possesses genotypic and phenotypic markers characteristic of a germinal center B-cell origin. Mod Pathol 19(2):299–306

    Article  PubMed  CAS  Google Scholar 

  6. Catlin EA, Roberts JD Jr, Erana R et al (1999) Transplacental transmission of natural-killer-cell lymphoma. N Engl J Med 341(2):85–91

    Article  PubMed  CAS  Google Scholar 

  7. Cecalupo AJ, Frankel LS, Sullivan MP (1982) Pelvic and ovarian extramedullary leukemic relapse in young girls. Cancer 50:587–593

    Article  PubMed  CAS  Google Scholar 

  8. Chan JK, Loizzi V, Magistris A et al (2005) Clinicopathologic features of six cases of primary cervical lymphoma. Am J Obstet Gynecol 193(3 Pt 1):866–872

    Article  PubMed  Google Scholar 

  9. Chandy L, Kumar L, Dawar R (1998) Non-Hodgkin’s lymphoma presenting as a primary lesion in uterine cervix: case report. J Obstet Gynaecol Res 24(3):183–187

    Article  PubMed  CAS  Google Scholar 

  10. Chishima F, Hayakawa S, Ohta Y et al (2006) Ovarian Burkitt’s lymphoma diagnosed by a combination of clinical features, morphology, immunophenotype, and molecular findings and successfully managed with surgery and chemotherapy. Int J Gynecol Cancer 16(Suppl 1):337–343

    Article  PubMed  Google Scholar 

  11. Cohn DE, Resnick KE, Eaton LA et al (2007) Non-Hodgkin’s lymphoma mimicking gynecological malignancies of the vagina and cervix: a report of four cases. Int J Gynecol Cancer 17(1):274–279

    Article  PubMed  CAS  Google Scholar 

  12. de Leval L, Ferry J, Falini B et al (2001) Expression of bcl-6 and CD10 in primary mediastinal large cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol 25(10):1277–1282

    Article  PubMed  Google Scholar 

  13. Diebold J, Jaffe E, Raphael M et al (2001) Burkitt’s lymphoma. In: Jaffe E et al (eds) Pathology and genetics: tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 181–184

    Google Scholar 

  14. Dimopoulos MA, Daliani D, Pugh W et al (1997) Primary ovarian non-Hodgkin’s lymphoma: outcome after treatment with combination chemotherapy. Gynecol Oncol 64:446–450

    Article  PubMed  CAS  Google Scholar 

  15. Domingo S, Perales A, Torres V et al (2004) Epstein-Barr virus positivity in primary vaginal lymphoma. Gynecol Oncol 95(3):719–721

    Article  PubMed  CAS  Google Scholar 

  16. Drinkard LC, Waggoner S, Stein RN et al (1995) Acute myelomonocytic leukemia with abnormal eosinophils presenting as an ovarian mass: a report of two cases and a review of the literature. Gynecol Oncol 56:307–311

    Article  PubMed  CAS  Google Scholar 

  17. Dursun P, Gultekin M, Bozdag G et al (2005) Primary cervical lymphoma: report of two cases and review of the literature. Gynecol Oncol 98(3):484–489

    Article  PubMed  Google Scholar 

  18. Ersahin C, Omeroglu G, Potkul RK et al (2007) Myeloid sarcoma of the vulva as the presenting symptom in a patient with acute myeloid leukemia. Gynecol Oncol 106(1):259–261

    Article  PubMed  Google Scholar 

  19. Ferry JA, Harris NL, Scully RE (1989) Leiomyomas with lymphoid infiltration simulating lymphoma. A report of 7 cases. Int J Gynecol Pathol 8:263–270

    Article  PubMed  CAS  Google Scholar 

  20. Ferry JA, Young RH (1991) Malignant lymphoma, pseudolymphoma and hematopoietic disorders of the female genital tract. Pathol Annu 26(Pt 1):227–263

    PubMed  Google Scholar 

  21. Ferry J, Young R (1997) Malignant lymphoma of the genitourinary tract. Curr Diagn Pathol 4:145–169

    Article  Google Scholar 

  22. Freeman C, Berg J, Cutler S (1972) Occurrence and prognosis of extranodal lymphomas. Cancer 29(1):252–260

    Article  PubMed  CAS  Google Scholar 

  23. Frey NV, Svoboda J, Andreadis C et al (2006) Primary lymphomas of the cervix and uterus: the University of Pennsylvania’s experience and a review of the literature. Leuk Lymphoma 47(9):1894–1901

    Article  PubMed  Google Scholar 

  24. Gaffan J, Herbertson R, Davis P et al (2004) Bilateral peripheral T-cell lymphoma of the fallopian tubes. Gynecol Oncol 95(3):736–738

    Article  PubMed  Google Scholar 

  25. Garavaglia E, Taccagni G, Montoli S et al (2005) Primary stage I-IIE non-Hodgkin’s lymphoma of uterine cervix and upper vagina: evidence for a conservative approach in a study on three patients. Gynecol Oncol 97(1):214–218

    Article  PubMed  Google Scholar 

  26. Garcia MG, Deavers MT, Knoblock RJ et al (2006) Myeloid sarcoma involving the gynecologic tract: a report of 11 cases and review of the literature. Am J Clin Pathol 125(5):783–790

    Article  PubMed  Google Scholar 

  27. Hachisuga T, Ookuma Y, Fakuda K et al (1992) Detection of Epstein-Barr virus DNA from a lymphoma-like lesion of the uterine cervix. Gynecol Oncol 46:69–73

    Article  PubMed  CAS  Google Scholar 

  28. Harris NL, Scully RE (1984) Malignant lymphoma and granulocytic sarcoma of the uterus and vagina. A clinicopathologic analysis of 27 cases. Cancer 53:2530–2545

    Article  PubMed  CAS  Google Scholar 

  29. Hernandez JA, Navarro JT, Rozman M et al (2002) Primary myeloid sarcoma of the gynecologic tract: a report of two cases progressing to acute myeloid leukemia. Leuk Lymphoma 43(11):2151–2153

    Article  PubMed  Google Scholar 

  30. Iliya FA, Muggia FM, O’Leary JA et al (1968) Gynecologic manifestations of reticulum cell sarcoma. Obstet Gynecol 31:266–269

    Article  PubMed  CAS  Google Scholar 

  31. Imrie KR, Kovass MJ, Selby D et al (1995) Isolated chloroma: the effect of early antileukemic therapy. Ann Intern Med 123(5):351–353

    PubMed  CAS  Google Scholar 

  32. Issa PY, Salem PA, Brihi E et al (1980) Eosinophilic granuloma with involvement of the female genitalia. Am J Obstet Gynecol 137:608–612

    PubMed  CAS  Google Scholar 

  33. Iyengar P, Deodhare S (2004) Primary extranodal marginal zone B-cell lymphoma of MALT type of the endometrium. Gynecol Oncol 93(1):238–241

    Article  PubMed  Google Scholar 

  34. Jackisch C, Louwen F, Schwenkhagen A et al (2003) Lung cancer during pregnancy involving the products of conception and a review of the literature. Arch Gynecol Obstet 268(2):69–77

    PubMed  Google Scholar 

  35. Kahlifa M, Buckstein R, Perez-Ordonez B (2003) Sarcomatoid variant of B-cell lymphoma of the uterine cervix. Int J Gynecol Pathol 22(3):289–293

    Article  PubMed  Google Scholar 

  36. Kaplan EJ, Chadburn A, Caputo TA (1996) Case report. HIV-related primary non-Hodgkin's lymphoma of the vulva. Gynecol Oncol 61:131–138

    Article  PubMed  CAS  Google Scholar 

  37. Kaplan MA, Jacobson JO, Ferry JA et al (1993) T cell lymphoma of the vulva with erythrophagocytosis in a renal allograft recipient. Am J Surg Pathol 17:842–849

    Article  PubMed  CAS  Google Scholar 

  38. Kawauchi S, Fukuma F, Morioka H et al (2002) Malignant lymphoma arising as a primary tumor of the uterine corpus. Pathol Int 52(5–6):423–424

    Article  PubMed  Google Scholar 

  39. Kirk CM, Naumann RW, Hartmann CJ et al (2001) Primary endometrial T-cell lymphoma. A case report. Am J Clin Pathol 115(4):561–566

    Article  PubMed  CAS  Google Scholar 

  40. Kosari F, Daneshbod Y, Parwaresch R et al (2005) Lymphomas of the female genital tract: a study of 186 cases and review of the literature. Am J Surg Pathol 29(11):1512–1520

    Article  PubMed  Google Scholar 

  41. Lagoo AS, Robboy SJ (2006) Lymphoma of the female genital tract: current status. Int J Gynecol Pathol 25(1):1–21

    Article  PubMed  Google Scholar 

  42. Lanjewar D, Dongaonkar D (2006) HIV-associated primary non-Hodgkin's lymphoma of ovary: a case report. Gynecol Oncol 102(3):590–592

    Article  PubMed  CAS  Google Scholar 

  43. Leoncini L, Raphael M, Stein H et al (2008) Burkitt’s lymphoma. In: Swerdlow S et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 262–264

    Google Scholar 

  44. Lieberman PH, Jones CR, Steinman RM et al (1996) Langerhans cells (eosinophilic) granulomatosis. Am J Surg Pathol 20:519–552

    Article  PubMed  CAS  Google Scholar 

  45. Liu PI, Ishimaru T, McGregor DH et al (1973) Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki 1949–1969. Cancer 31:948–955

    Article  PubMed  CAS  Google Scholar 

  46. Lyman MD, Neuhauser TS (2002) Precursor T-cell acute lymphoblastic leukemia/lymphoma involving the uterine cervix, myometrium, endometrium, and appendix. Ann Diagn Pathol 6(2):125–128

    Article  PubMed  Google Scholar 

  47. Ma J, Shi Q, Zhou X et al (2007) Lymphoma-like lesion of the uterine cervix: report of 12 cases of a rare entity. Int J Gynecol Pathol 26(2):194–198

    Article  PubMed  Google Scholar 

  48. Macleod C, Palmer A, Findlay M (1998) Primary non-Hodgkin’s lymphoma of the vulva: a case report. Int J Gynecol Cancer 8:504–508

    Article  Google Scholar 

  49. Magloire LK, Pettker CM, Buhimschi CS et al (2006) Burkitt’s lymphoma of the ovary in pregnancy. Obstet Gynecol 108(3 Pt 2):743–745

    Article  PubMed  Google Scholar 

  50. Makarewicz R, Kuzminska A (1995) Non-Hodgkin’s lymphoma of the uterine cervix: a report of three patients. Clin Oncol (R Coll Radiol) 7:198–199

    Article  CAS  Google Scholar 

  51. Mansouri H, Sifat H, Gaye M et al (2000) Primary malignant lymphoma of the ovary: an unusual presentation of a rare disease. Eur J Gynaec Oncol 21(6):616–618

    CAS  Google Scholar 

  52. Maruko K, Maeda T, Kamitomo M et al (2004) Transplacental transmission of maternal B-cell lymphoma. Am J Obstet Gynecol 191(1):380–381

    Article  PubMed  Google Scholar 

  53. McKelvey A, McKenna D, McManus D et al (2003) A case of lymphoma occurring in an ovarian teratoma. Gynecol Oncol 90(2):474–477

    Article  PubMed  Google Scholar 

  54. Meguerian-Bedoyan Z, Lamant L, Hopfner C et al (1997) Anaplastic large cell lymphoma of maternal origin involving the placenta: case report and literature survey. Am J Surg Pathol 21(10):1236–1241

    Article  PubMed  CAS  Google Scholar 

  55. Meis JM, Butler JJ, Osborne BM et al (1986) Granulocytic sarcoma in nonleukemic patients. Cancer 58:2697–2709

    Article  PubMed  CAS  Google Scholar 

  56. Montero AJ, Diaz-Montero CM, Malpica A et al (2003) Langerhans cell histiocytosis of the female genital tract: a literature review. Int J Gynecol Cancer 13(3):381–388

    Article  PubMed  CAS  Google Scholar 

  57. Murase T, Inagaki H, Takagi N et al (2002) Nasal NK-cell lymphoma followed by relapse in the uterine cervix. Leuk Lymphoma 43(1):203–206

    Article  PubMed  Google Scholar 

  58. Nagarsheth NP, Kalir T, Rahaman J (2005) Post-transplant lymphoproliferative disorder of the cervix. Gynecol Oncol 97(1):271–275

    Article  PubMed  Google Scholar 

  59. Nasu K, Yoshimatsu J, Urata K et al (1998) A case of primary non-Hodgkin’s lymphoma of the uterine cervix treated by combination chemotherapy (THP-COP). J Obstet Gynaecol Res 24(2):157–160

    Article  PubMed  CAS  Google Scholar 

  60. Neiman RS, Barcos M, Berard C et al (1981) Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 48:1426–1437

    Article  PubMed  CAS  Google Scholar 

  61. Neuhauser TS, Tavassoli FA, Abbondanzo SL (2000) Follicle center lymphoma involving the female genital tract: a morphologic and molecular genetic study of three cases. Ann Diagn Pathol 4(5):293–299

    Article  PubMed  CAS  Google Scholar 

  62. Nishi Y, Suzuki S, Otsubo Y et al (2000) B-cell-type malignant lymphoma with placental involvement. J Obstet Gynaecol Res 26(1):39–43

    Article  PubMed  CAS  Google Scholar 

  63. Noack F, Lange K, Lehmann V et al (2002) Primary extranodal marginal zone B-cell lymphoma of the fallopian tube. Gynecol Oncol 86(3):384–386

    Article  PubMed  Google Scholar 

  64. Nomura S, Ishii K, Shimamoto Y et al (2006) Burkitt’s lymphoma of the uterus in a human T lymphotropic virus type-1 carrier. Intern Med 45(4):215–217

    Article  PubMed  Google Scholar 

  65. Ohmori T, Wakamoto R, Lu LM et al (2002) Immunohistochemical study of a case of uterine leiomyoma showing massive lymphoid infiltration and localized vasculitis after LH-RH derivant treatment. Histopathology 41(3):276–277

    PubMed  CAS  Google Scholar 

  66. Oliva E, Ferry JA, Young RH et al (1997) Granulocytic sarcoma of the female genital tract. A clinicopathologic study of 11 cases. Am J Surg Pathol 21:1156–1165

    Article  PubMed  CAS  Google Scholar 

  67. Osborne BM, Robboy SJ (1983) Lymphomas or leukemia presenting as ovarian tumors. An analysis of 42 cases. Cancer 52:1933–1943

    Article  PubMed  CAS  Google Scholar 

  68. Padula A, Medeiros LJ, Silva EG et al (2004) Isolated vulvar Langerhans cell histiocytosis: report of two cases. Int J Gynecol Pathol 23(3):278–283

    Article  PubMed  Google Scholar 

  69. Paik SS, Oh YH, Jang KS et al (2004) Uterine leiomyoma with massive lymphoid infiltration: case report and review of the literature. Pathol Int 54(5):343–348

    Article  PubMed  Google Scholar 

  70. Pathak B, Bruchim I, Brisson ML et al (2005) Granulocytic sarcoma presenting as tumors of the cervix. Gynecol Oncol 98(3):493–497

    Article  PubMed  Google Scholar 

  71. Perren T, Farrant M, McCarthy K et al (1992) Lymphomas of the cervix and upper vagina: a report of five cases and a review of the literature. Gynecol Oncol 44:87–95

    Article  PubMed  CAS  Google Scholar 

  72. Prevot S, Hugol D, Audouin J et al (1992) Primary non Hodgkin’s malignant lymphoma of the vagina. Report of 3 cases with review of the literature. Path Res Pract 188:78–85

    Article  PubMed  CAS  Google Scholar 

  73. Pullarkat V, Veliz L, Chang K et al (2007) Therapy-related, mixed-lineage leukaemia translocation-positive, monoblastic myeloid sarcoma of the uterus. J Clin Pathol 60(5):562–564

    Article  PubMed  Google Scholar 

  74. Rappaport H (1966) Tumors of the hematopoietic system, Atlas of tumor pathology, Series I, Fascicle 8. Washington, DC, Armed Forces Institute of Pathology

    Google Scholar 

  75. Saglam A, Guler G, Taskin M et al (2005) Uterine leiomyoma with prominent lymphoid infiltrate. Int J Gynecol Cancer 15(1):167–170

    Article  PubMed  CAS  Google Scholar 

  76. Sakurai N, Tateoka K, Taguchi J et al (2008) Primary precursor B-cell lymphoblastic lymphoma of the ovary: case report and review of the literature. Int J Gynecol Pathol 27(3):412–417

    Article  PubMed  Google Scholar 

  77. Santillan A, Montero AJ, Kavanagh JJ et al (2003) Vulvar Langerhans cell histiocytosis: a case report and review of the literature. Gynecol Oncol 91(1):241–246

    Article  PubMed  Google Scholar 

  78. Scully RE (1979) Tumors of the ovary and maldeveloped gonads, Atlas of tumor pathology, Series 2, Fascicle 16. Armed Forces Institute of Pathology, Washington, DC, pp 117–127

    Google Scholar 

  79. Shulman LN, Hitt RA, Ferry JA (2008) Case records of the Massachusetts General Hospital. Case 4-2008. A 33-year-old pregnant woman with swelling of the left breast and shortness of breath. N Engl J Med 358(5):513–523

    Article  PubMed  CAS  Google Scholar 

  80. Spahr J, Behm FG, Schneider V (1982) Preleukemic granulocytic sarcoma of cervix and vagina. Initial manifestation by cytology. Acta Cytol 26:55–60

    PubMed  CAS  Google Scholar 

  81. Sur M, Ross C, Moens F et al (2005) Intravascular large B-cell lymphoma of the uterus: a diagnostic challenge. Int J Gynecol Pathol 24(2):201–203

    Article  PubMed  Google Scholar 

  82. Tjalma W, Van de Velde A, Schroyens W (2002) Primary non-Hodgkin’s lymphoma in Bartholin’s gland. Gynecol Oncol 87(3):308–309

    Article  PubMed  Google Scholar 

  83. Valeri RM, Ibrahim N, Sheaff MT (2002) Extramedullary hematopoiesis in the endometrium. Int J Gynecol Pathol 21(2):178–181

    Article  PubMed  Google Scholar 

  84. van de Rijn M, Kamel O, Chang P et al (1997) Primary low grade endometrial B-cell lymphoma. Am J Surg Pathol 21:187–194

    Article  PubMed  Google Scholar 

  85. van der Velden VH, Willemse MJ, Mulder MF et al (2001) Clearance of maternal leukaemic cells in a neonate. Br J Haematol 114(1):104–106

    Article  PubMed  Google Scholar 

  86. Vang R, Medeiros LJ, Fuller GN et al (2001) Non-Hodgkin’s lymphoma involving the gynecologic tract: a review of 88 cases. Adv Anat Pathol 8(4):200–217

    Article  PubMed  CAS  Google Scholar 

  87. Vang R, Medeiros LJ, Ha CS et al (2000) Non-Hodgkin’s lymphomas involving the uterus: a clinicopathologic analysis of 26 cases. Mod Pathol 13(1):19–28

    Article  PubMed  CAS  Google Scholar 

  88. Vang R, Medeiros L, Malpica A et al (2000) Non-Hodgkin’s lymphoma involving the vulva. Int J Gynecol Pathol 19(3):236–242

    Article  PubMed  CAS  Google Scholar 

  89. Vang R, Medeiros L, Silva E et al (2000) Non-Hodgkin’s lymphoma involving the vagina. A clinicopathologic analysis of 14 patients. Am J Surg Pathol 24(5):719–725

    Article  PubMed  CAS  Google Scholar 

  90. Vang R, Medeiros L, Warnke R et al (2001) Ovarian non-Hodgkin’s lymphoma: a clinicopathologic study of eight primary cases. Mod Pathol 14(11):1093–1099

    Article  PubMed  CAS  Google Scholar 

  91. Venizelos ID, Mandala E, Tatsiou ZA et al (2006) Primary Langerhans cell histiocytosis of the vulva. Int J Gynecol Pathol 25(1):48–51

    Article  PubMed  Google Scholar 

  92. Weiss L, Grogan T, Muller-Hermelink HK et al (2001) Langerhans cell histiocytosis. In: Jaffe E et al (eds) Pathology and genetics: tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon, pp 280–282

    Google Scholar 

  93. Wyld PH, Lilleyman JS (1983) Ovarian disease in childhood lymphoblastic leukemia. Acta Haematol 69:278–280

    Article  PubMed  CAS  Google Scholar 

  94. Yamada N, Uchida R, Fuchida S et al (2005) CD5+ Epstein-Barr virus-positive intravascular large B-cell lymphoma in the uterus co-existing with huge myoma. Am J Hematol 78(3):221–224

    Article  PubMed  Google Scholar 

  95. Yoshinaga K, Akahira J, Niikura H et al (2004) A case of primary mucosa-associated lymphoid tissue lymphoma of the vagina. Hum Pathol 35(9):1164–1166

    Article  PubMed  Google Scholar 

  96. Young RH, Harris NL, Scully RE (1985) Lymphoma-like lesions of the lower female genital tract: a report of 16 cases. Int J Gynecol Pathol 4:289–299

    Article  PubMed  CAS  Google Scholar 

  97. Zinzani P, Martelli M, Bertini M et al (2002) Induction chemotherapy strategies for primary mediastinal large B-cell lymphoma with sclerosis: a retrospective multinational study on 426 previously untreated patients. Haematologica 87:1258–1264

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judith A. Ferry .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this entry

Cite this entry

Ferry, J.A. (2011). Hematologic Neoplasms and Selected Tumor-Like Lesions Involving the Female Reproductive Organs. In: Kurman, R.J., Ellenson, L.H., Ronnett, B.M. (eds) Blaustein’s Pathology of the Female Genital Tract. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-0489-8_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-0489-8_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-0488-1

  • Online ISBN: 978-1-4419-0489-8

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics