eMedicine Specialties > Dermatology > Lymphoma and Related Processes

Lymphomatoid Papulosis: Differential Diagnoses & Workup

Author: John A Zic, MD, Director of VU Cutaneous Lymphoma Clinic, Assistant Professor of Medicine Dermatology, Vanderbilt University Medical Center
Contributor Information and Disclosures

Updated: Dec 16, 2009

Differential Diagnoses

Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma
Lymphocytoma Cutis
Cutaneous T-Cell Lymphoma
Milia
Folliculitis
Miliaria
Insect Bites
Scabies
Langerhans Cell Histiocytosis
Leukemia Cutis

Other Problems to Be Considered

Papular drug eruption
Papular variant of MF
Pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease)
Primary or secondary cutaneous B-cell lymphoma
Primary or secondary cutaneous HD
Hydroa-vacciniforme – like primary cutaneous T-cell lymphoma

Treatments reportedly associated with lymphomatoid papulosis include allogenic stem cell transplantation, minocycline therapy, and efalizumab.12,13,14

Workup

Laboratory Studies

  • No WBC count or serum chemistry abnormalities are expected in lymphomatoid papulosis (LyP) patients.

Imaging Studies

  • de Souza et al recommend that a search for a thymoma be conducted after describing a patient whose lymphomatoid papulosis resolved after having a type AB thymoma surgically excised.15

Procedures

  • Obtain skin biopsy specimens from 2 or more fully developed inflammatory papules without necrosis or excoriation.
  • Skin biopsy is indicated to confirm the diagnosis and to exclude primary cutaneous ALCL, if possible. Because histologic distinction may be difficult, consult a dermatopathologist with experience in diagnosing lymphoproliferative skin disorders.

Histologic Findings

Upon low-power histologic examination, lymphomatoid papulosis shows a wedge-shaped dense dermal infiltrate of lymphoid cells with numerous eosinophils, neutrophils, and atypical lymphocytes. As much as 50% of the infiltrate shows the atypical lymphocytes. Epidermotropism of lymphoid cells may occur. Dermal vessels may show endothelial swelling, fibrin deposition, and red blood cell extravasation.

Histologically, lymphomatoid papulosis is divided into the following 3 subtypes16,17 :

  • Type A is characterized by large (25-40 µm) CD30+ atypical cells intermingled with a prominent inflammatory infiltrate. The large tumor cells have polymorphic convoluted nuclei with a minimum of 1 prominent nucleolus and resemble Reed-Sternberg cells when binucleate, as is seen in HD. Type A lymphomatoid papulosis is the most common histologic variant and accounts for 75% of all lymphomatoid papulosis specimens.
  • Type B is characterized by smaller (8-15 µm) atypical cells with hyperchromatic cerebriform nuclei resembling the atypical lymphocytes in MF. CD30+ large cells are rare, but epidermotropism is more common in this variant. There is some concern that Type B lymphomatoid papulosis may be better classified as a papular variant of MF.
  • Type C (diffuse large cell type) is characterized by sheets of CD30+ anaplastic large cells indistinguishable from ALCL, with the exception of the minimal subcutaneous invasion. These lesions resolve spontaneously and are therefore classified as lymphomatoid papulosis; however, some authorities view this histologic variant as borderline ALCL or, perhaps, pcALCL.18
Uncommonly, patients may have more than one histologic subtype of lymphomatoid papulosis or other recently described associated histologic patterns.

Immunophenotyping and molecular findings
CD 30 (Ki-1) expression is characteristic. The atypical lymphocyte is predominantly a CD4+ helper/inducer T cell with HLA-DR and interleukin 2 receptor (CD25) expression and variable loss of CD5 and/or CD7 antigen expression. CD30+ expression is characteristic, but, paradoxically, the small tumor cells in lymphomatoid papulosis type B are usually CD30 negative. Tumor cells in lymphomatoid papulosis may express cytotoxic molecules such as CD56, TIA-1, and granzyme B. CXCR3, a Th1 cell marker, is expressed in up to 85% of lymphomatoid papulosis cases. Emergence of CCR4 positivity, a Th2 marker common in pcALCL, has been hypothesized as a risk factor for malignant progression. CD8 lymphomatoid papulosis has been noted in the literature and may represent a distinct clinical entity.

Clonality in lymphomatoid papulosis is controversial, and not all cases of lymphomatoid papulosis in the literature are clonal as detected by analysis of T-cell antigen receptor genes. However, monoclonal rearrangement of the T-cell antigen receptor has been detected in 40-90% of lymphomatoid papulosis lesions, and identical clones have been demonstrated in the peripheral blood cells of patients with severe disease. One investigation suggested that the cell infiltrate in lymphomatoid papulosis comprises a mixture of polyclonal large atypical cells (CD30+) and smaller monoclonal T cells (CD30-negative). The (2;5)(p23;q35) translocation is not detected.

Staging

No staging scheme has been described for lymphomatoid papulosis.

More on Lymphomatoid Papulosis

Overview: Lymphomatoid Papulosis
Differential Diagnoses & Workup: Lymphomatoid Papulosis
Treatment & Medication: Lymphomatoid Papulosis
Follow-up: Lymphomatoid Papulosis
Multimedia: Lymphomatoid Papulosis
References
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References

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Further Reading

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Keywords

lymphomatoid papulosis, Macaulay disease, Macaulay's disease, LyP, T-cell lymphoma, T cell lymphoma, cutaneous lymphoma, mycosis fungoides, MF, Hodgkin disease, Hodgkin lymphoma, Hodgkin's disease, Hodgkin's lymphoma, HD, lymphoproliferative disease, lymphoproliferative disorder, LPD, anaplastic large cell lymphoma, ALCL, primary cutaneous anaplastic large cell lymphoma, pcALCL

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Contributor Information and Disclosures

Author

John A Zic, MD, Director of VU Cutaneous Lymphoma Clinic, Assistant Professor of Medicine Dermatology, Vanderbilt University Medical Center
John A Zic, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Gregory J Raugi, MD, PhD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington at Seattle; Chief, Dermatology Section, Primary and Specialty Care Service, Veterans Administration Medical Center of Seattle
Gregory J Raugi, MD, PhD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, 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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