eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma: Differential Diagnoses & Workup

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: Nov 30, 2009

Differential Diagnoses

Lymphomatoid Papulosis

Other Problems to Be Considered

Primary CD30- T-cell large cell lymphoma (T-LCL)
Primary cutaneous Hodgkin disease
Granulocytic sarcoma
Viral infection

Workup

Laboratory Studies

  • Molecular diagnostic techniques and cytogenetic studies for cutaneous CD30+ (Ki-1) anaplastic large-cell lymphoma (cutaneous CD30+ ALCL)
    • Most cases have clonally rearranged T-cell receptor genes.
    • The t(2;5) translocation has shown a high degree of association with systemic forms of CD30+ ALCL; however, it is relatively rare in the primary cutaneous form of ALCL.
    • Reverse transcriptase-polymerase chain reaction (RT-PCR) can be performed to detect the t(2;5) translocation for diagnostic purposes or for monitoring of minimal residual disease.

Imaging Studies

  • CT scan of the chest and the abdomen may be performed for staging of lymphoma and for differentiating the primary cutaneous form from the systemic form involving the skin. The latter has systemic lymphadenopathy other than regional lymphadenopathy associated with skin lesions.

Procedures

  • A skin biopsy may be performed.
  • A bone marrow biopsy may be performed for staging.

Histologic Findings

Cutaneous CD30+ (Ki-1) anaplastic large-cell lymphoma (cutaneous CD30+ ALCL) consists of diffuse nonepidermotropic infiltrates with cohesive sheets of large CD30+ tumor cells. In most cases, the tumor cells may have the characteristic morphology of anaplastic cells, showing round, oval, or irregularly shaped nuclei; prominent (eosinophilic) nucleoli; and abundant cytoplasm. Less commonly, tumor cells have a pleomorphic or immunoblastic appearance. Reactive lymphocytes are often present at the periphery of the lesions. In some cases, numerous inflammatory cells (eg, T cells, eosinophils, neutrophils) and relatively few CD30+ cells may be observed (lymphomatoid papulosis [LyP]–like histology). Epidermal hyperplasia may be prominent in such cases.

Immunophenotypically, most neoplastic lymphocytes have a unique CD4+, CD8-, and cytotoxic T-cell phenotype (TIA-1 and granzyme B+), with variable loss of pan–T-cell antigens (eg, CD2, CD3, CD5).3 CD30 must be expressed by most (>75%) of the neoplastic cells. The neoplastic lymphocytes in the primary cutaneous form are usually epithelial membrane antigen (EMA) negative in contrast to the systemic form.

LyP and cutaneous CD30+ lymphoma are closely related conditions in which large atypical lymphocytes that have similar immunophenotypic features occur.

In LyP, the lesions are papules and nodules that spontaneously involute. Two polar histologic patterns (type A and type B) occur in which the large atypical cells resemble those of Hodgkin disease and mycosis fungoides, respectively, but, in many cases, features of both types are present, either separately or in the same lesions. Type C LyP includes lesions that show sheets of atypical mononuclear cells with little admixed inflammatory cells, a histologic picture that is difficult to separate from classic CD30+ ALCL. Variants of LyP include cases with a perifollicular distribution and those with lymphocytic vasculitis or dermal mucin deposits.

LyP is associated with a long benign course of frequent regression of papular lesions. The risk of developing a malignant lymphoma is approximately 10-20%.

A loss of response to transforming growth factor-beta, which normally dampens cellular proliferation, favors a diagnosis of CD30+ ALCL instead of LyP. A recent study shows that CCR3 was expressed by atypical lymphoid cells in 10 (83%) of 12 cases of ALCL, but in only 5 (38%) of 13 cases of LyP. CXCR3 was expressed in 11 (85%) of 13 cases of LyP, but in only 1 (8%) of 12 cases of ALCL. CCR4 was expressed in 11 (92%) of 12 cases of ALCL, but in only 2 (15%) of 13 cases of LyP. RANTES was strongly expressed by lymphoma cells in ALCL (11 [92%] of 12), but was weak or sporadic in LyP (7 [54%] of 13).4 These markers may be useful to differentiate ALCL from LyP in difficult cases. Lesions of LyP typically show clonal TCR rearrangements; therefore, this is not a useful test to differentiate between these entities.

The term borderline case refers to cases in which a discrepancy between the clinical features and the histologic appearance exists. These include cases with the clinical presentation of a CD30+ ALCL but with histologic features suggestive of LyP, and, conversely, cases with recurrent, self-healing skin lesions, that on histologic examination, show a rather uniform proliferation of large CD30+ tumor cells with only a few admixed inflammatory cells, which is characteristic of a CD30+ ALCL. The presence of these cases indicates that CD30+ ALCL and LyP are parts of a spectrum of primary cutaneous CD30+ lymphoproliferative disorders. The distinction between LyP and the primary cutaneous form of CD30+ ALCL is not always possible on the basis of histologic criteria. Thus, the clinical appearance and the course are used as decisive criteria for the definite diagnosis and the choice of treatment.

Primary CD30- T-LCL is generally associated with a poor prognosis.

Primary cutaneous Hodgkin disease probably does exist as a rare, often deep-seated, nodular disorder that usually has a good prognosis. Reed-Sternberg cells in Hodgkin disease are CD15+ in addition to CD30+.

The authors' observation indicates that CD30 may be positive in rare cases of granulocytic sarcoma, though the staining intensity is weaker than that seen in CD30+ ALCL.

CD30+ lymphocytes can be found in certain viral infections, such as human T-lymphotropic virus type I, HIV, hepatitis B and C viruses, Epstein-Barr virus, and Parapoxvirus infection.

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
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References

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  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. 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].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

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Further Reading

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Keywords

cutaneous CD30+ (Ki-1) anaplastic large-cell lymphoma, cutaneous CD30+ ALCL, cutaneous ALCL, 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

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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 for Clinical Pathology, 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 for Clinical Pathology, 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; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, 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, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Daniel S Loo, MD, Associate Professor of Dermatology, Residency Program Director, Department of Dermatology, Tufts Medical Center
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: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis  investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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