eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma

Author: Chung-Che Chang, MD, PhD, Medical Director and Program Director of Hematopathology, Associate Professor of Pathology, Department of Hematopathology, Methodist Hospital, Weil Medical College, Cornell University, Houston
Coauthor(s): Scott M Acker, MD, Associate Professor, Director of Dermatopathology, Departments of Dermatology and Pathology, University of Alabama at Birmingham
Contributor Information and Disclosures

Updated: Feb 27, 2007

Introduction

Background

Cutaneous CD30+ (Ki-1) anaplastic large-cell lymphoma (cutaneous CD30+ ALCL) is clinically and pathologically heterogeneous, leading to some difficulty in its diagnosis and classification. Expression of CD30 (an activation marker for B or T cells) in more than 75% of neoplastic cells characterizes this group of lymphoproliferative disorders.

Based on clinical manifestations, cutaneous CD30+ ALCL can be subdivided mainly into a primary cutaneous form without extracutaneous involvement at presentation or a systemic form with secondary skin involvement at presentation. The primary cutaneous form (see History) generally has a better prognosis than the systemic form with secondary skin involvement. Sometimes (in up to 25% of cases), spontaneous regression of the primary cutaneous form occurs despite high-grade anaplastic cytology of neoplastic lymphocytes.

Cutaneous CD30+ ALCL can be further classified into different groups according to histologic features (eg, pleomorphic, immunoblastic, monomorphic, small-cell predominant, Hodgkin disease–related, and other less common variants); immunophenotype (eg, T, null, B, rarely B and T); and other clinical features, such as ALCL arising in patients who are HIV positive and ALCL occurring after another lymphoproliferative process (eg, lymphomatoid papulosis, mycosis fungoides, Hodgkin disease). The primary cutaneous form is composed of predominantly anaplastic morphology type, though pleomorphic and immunoblastic morphology types can infrequently be seen.

Pathophysiology

Cytogenetic studies and subsequent cloning of the translocation t(2;5) have shown a high degree of association with systemic forms of CD30+ ALCL. This genetic abnormality is not specific for anaplastic morphologic features and is more common in the monomorphic and small-cell variants. However, the t(2;5) is relatively rare in the primary cutaneous form of ALCL. This points to a molecular etiology of primary cutaneous CD30+ ALCL distinct from that of extracutaneous (systemic form) CD30+ lymphoproliferative disease.

This translocation creates a novel fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced-stage disease and have tumors with a CD30+, T- or null-cell phenotype. It is less frequently detected in older patients and in ALCL of pleomorphic histology.

The neoplastic cells are CD30+ positive and typically have a T-helper phenotype (ie, CD3+, CD4+). Cells are usually CD8-. Pan–T-cell antigens may be partially lost. Monoclonal rearrangement of the TCR gene is observed in most cases. However, Bonzheim et al recently reported that only 2 (4%) of 47 ALCLs expressed TCR-beta protein. Moreover, both TCR-beta(+) ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable for the transduction of cognate TCR signals). Thus, defective expression of TCRs is a common characteristic of all types of ALCL, which may contribute to the dysregulation of intracellular signaling pathways controlling T-cell activation and survival.

CD30 is a protein in the tumor necrosis factor receptor superfamily. CD30 must be expressed in more than 75% of cells for the diagnosis. The primary cutaneous form is typically CD15-.

CD95 (FAS protein that induces apoptosis) expression is preferentially expressed at high levels in all primary cutaneous forms of CD30+ lymphomas and suggests that CD95 may play a role in the regression of CD30+ skin lesions.

No clear-cut distinction exists clinically or histologically between some expressions of lymphomatoid papulosis and the primary cutaneous form of CD30+ ALCL. This discrimination may be artificial in some cases because 10% of cases of lymphomatoid papulosis progress to the clear-cut primary cutaneous form of CD30+ ALCL.

Frequency

United States

The frequency of CD30+ ALCL in the United States is not known.

International

CD30+ ALCL comprise approximately 5% of all non-Hodgkin lymphoma (NHL). The primary cutaneous form of CD30+ ALCL makes up about 10% of the total primary cutaneous lymphoproliferative disorders and is the second most common primary cutaneous lymphoproliferative disorder after mycosis fungoides.

Mortality/Morbidity

The 5-year survival rate is 90% for the primary cutaneous form of CD30+ ALCL. The prognosis of the systemic form with secondary cutaneous involvement depends on the expression of the ALK protein. Patients with expression of ALK have a 5-year survival rate ranging from 70-80%. The 5-year survival rate in patients without ALK expression ranges from 15-30%.

Sex

The male-to-female ratio is 3:2.

Age

Patients with primary cutaneous forms of ALCL are generally older (median age, 61 y) than patients with the systemic form of ALCL (median age, 24 y) and, in contrast to the latter group, do not show a bimodal age distribution.

Clinical

History

  • The primary cutaneous form is defined by skin-only involvement without systemic dissemination at presentation. Draining regional lymph node involvement occurs in approximately 25% of patients with only skin lesions. Whether the patients only showing draining regional lymph node involvement should be considered to have a primary cutaneous form remains controversial.
  • Patients with widespread systemic and cutaneous disease at first presentation should be considered to have the systemic form with skin involvement.

Physical

  • Patients usually present with solitary or ulcerating nodules or tumors.
  • Lesions are typically reddish brown and indurated.
  • Involvement of the draining regional lymph nodes occurs in approximately 25% of patients. (This does not appear to be associated with a worse prognosis.)

Causes

In the systemic form of CD30+ ALCL, t(2;5), resulting in a novel fusion protein (NPM-ALK), may play an important role for the development of disease. The primary cutaneous form, however, does not commonly show this translocation, and the etiology remains unknown.

More on Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma

Overview: Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
Differential Diagnoses & Workup: Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
Treatment & Medication: Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
Follow-up: Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
References
[ CLOSE WINDOW ]

References

  1. Bekkenk MW, Geelen FA, van Voorst Vader PC, Heule F, Geerts ML, van Vloten WA, et al. Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment. Blood. Jun 15 2000;95(12):3653-61. [Medline].

  2. Bonzheim I, Geissinger E, Roth S, Zettl A, Marx A, Rosenwald A, et al. Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling. Blood. Nov 15 2004;104(10):3358-60. [Medline].

  3. de Bruin PC, Beljaards RC, van Heerde P, Van Der Valk P, Noorduyn LA, Van Krieken JH, et al. Differences in clinical behaviour and immunophenotype between primary cutaneous and primary nodal anaplastic large cell lymphoma of T-cell or null cell phenotype. Histopathology. Aug 1993;23(2):127-35. [Medline].

  4. Duncan LM. Cutaneous lymphoma. Understanding the new classification schemes. Dermatol Clin. Jul 1999;17(3):569-92. [Medline].

  5. Fanin R, Sperotto A, Silvestri F, Cerno M, Geromin A, Stocchi R, et al. The therapy of primary adult systemic CD30-positive anaplastic large cell lymphoma: results of 40 cases treated in a single center. Leuk Lymphoma. Sep 1999;35(1-2):159-69. [Medline].

  6. Kempf W, Dummer R, Burg G. Approach to lymphoproliferative infiltrates of the skin. The difficult lesions. Am J Clin Pathol. Jan 1999;111(1 Suppl 1):S84-93. [Medline].

  7. Kinney MC, Kadin ME. The pathologic and clinical spectrum of anaplastic large cell lymphoma and correlation with ALK gene dysregulation. Am J Clin Pathol. Jan 1999;111(1 Suppl 1):S56-67. [Medline].

  8. Kummer JA, Vermeer MH, Dukers D, Meijer CJ, Willemze R. Most primary cutaneous CD30-positive lymphoproliferative disorders have a CD4-positive cytotoxic T-cell phenotype. J Invest Dermatol. Nov 1997;109(5):636-40. [Medline].

  9. LeBoit PE. Lymphomatoid papulosis and cutaneous CD30+ lymphoma. Am J Dermatopathol. Jun 1996;18(3):221-35. [Medline].

  10. Mori M, Manuelli C, Pimpinelli N, Mavilia C, Maggi E, Santucci M, et al. CD30-CD30 ligand interaction in primary cutaneous CD30(+) T-cell lymphomas: A clue to the pathophysiology of clinical regression. Blood. Nov 1 1999;94(9):3077-83. [Medline].

  11. Paulli M, Berti E, Boveri E, Kindl S, Bonoldi E, Gambini C, et al. Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily. Hum Pathol. Nov 1998;29(11):1223-30. [Medline].

  12. Paulli M, Berti E, Rosso R, Boveri E, Kindl S, Klersy C, et al. CD30/Ki-1-positive lymphoproliferative disorders of the skin--clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group. J Clin Oncol. Jun 1995;13(6):1343-54. [Medline].

  13. Shehan JM, Kalaaji AN, Markovic SN, Ahmed I. Management of multifocal primary cutaneous CD30 anaplastic large cell lymphoma. J Am Acad Dermatol. Jul 2004;51(1):103-10. [Medline].

  14. Tomaszewski MM, Lupton GP, Krishnan J, May DL. A comparison of clinical, morphological and immunohistochemical features of lymphomatoid papulosis and primary cutaneous CD30(Ki-1)-positive anaplastic large cell lymphoma. J Cutan Pathol. Aug 1995;22(4):310-8. [Medline].

  15. Vergier B, Beylot-Barry M, Pulford K, Michel P, Bosq J, de Muret A, et al. Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases. Am J Surg Pathol. Oct 1998;22(10):1192-202. [Medline].

  16. Vonderheid EC, Sajjadian A, Kadin ME. Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders. J Am Acad Dermatol. Mar 1996;34(3):470-81. [Medline].

  17. Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30 (Ki-1)-positive lymphoproliferative disorders. A proposal for classification and guidelines for management and treatment. J Am Acad Dermatol. Jun 1993;28(6):973-80. [Medline].

  18. Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood. Jul 1 1997;90(1):354-71. [Medline].

  19. Yamaguchi T, Ohshima K, Karube K, Kawano R, Nakayama J, Suzumiya J, et al. Expression of chemokines and chemokine receptors in cutaneous CD30+ lymphoproliferative disorders. Br J Dermatol. May 2006;154(5):904-9. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

CD30+ ALCL, regressing atypical histiocytosis, RAH, CD30+ cutaneous large T-cell lymphoma, pseudo-Hodgkin disease, pseudo-Hodgkin's disease, non-Hodgkin lymphoma, NHL, pseudo-Hodgkin lymphoma

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Chung-Che Chang, MD, PhD, Medical Director and Program Director of Hematopathology, Associate Professor of Pathology, Department of Hematopathology, Methodist Hospital, Weil Medical College, Cornell University, Houston
Chung-Che Chang, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Clinical Pathologists, College of American Pathologists, and International Academy of Pathology
Disclosure: Nothing to disclose.

Coauthor(s)

Scott M Acker, MD, Associate Professor, Director of Dermatopathology, Departments of Dermatology and Pathology, University of Alabama at Birmingham
Scott M Acker, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Clinical Pathologists, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: none None None

Managing Editor

Daniel S Loo, MD, Associate Professor, Residency Program Director, Department of Dermatology, Boston University School of Medicine
Daniel S Loo, MD is a member of the following medical societies: American Academy of Dermatology and Association of Professors of Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.