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Cutaneous Pseudolymphoma Workup

  • Author: Christine J Ko, MD; Chief Editor: William D James, MD  more...
 
Updated: May 17, 2016
 

Approach Considerations

Immunohistochemical stains are usually required to facilitate differentiation between pseudolymphomatous eruptions and lymphoma. Although none of these tests is perfectly specific or diagnostic alone, they may be particularly helpful in supporting or refuting a diagnosis of lymphoma in the appropriate clinicopathologic context.  PD1+ cells are more common in pseudolymphomatous folliculitis compared with marginal zone lymphoma.[23]

Before advances in immunophenotyping and gene rearrangement analysis, the diagnosis was based on histologic findings and benign clinical behavior. Clinical follow up for 5 years following initial skin biopsy had been accepted as confirmation of the diagnosis[9] ; however, both drug-induced pseudolymphoma and variants of cutaneous B-cell lymphoma, such as marginal zone, may have a similar indolent course.

In patients with borrelial pseudolymphoma, antibodies to Borrelia burgdorferi may be identified in 50% of cases. Additionally, the organism may be identified in tissue via polymerase chain reaction (PCR) analysis.

Routine laboratory results most often remain within the reference ranges and play a limited role in diagnosis.[5]

CBC count

Leukocytosis with eosinophilia may occur in severe cases.

Liver-associated enzymes

Transaminitis has been reported; however, it is more prevalent in drug-induced hypersensitivity syndrome and, when present, confers a worse prognosis, with one study reporting 10-50% mortality with severe hepatitis.[2]

T-cell receptor gene rearrangement studies

PCR-based assessment of T-cell receptor gamma genes may be used to reveal a dominant clone of T-cells within a population. Because T-cell pseudolymphomas are most often polyclonal, demonstration of such a dominant clone favors a diagnosis of CTCL. Unfortunately, both rare monoclonal T-cell pseudolymphomas and polyclonal CTCL cases have been reported, thus decreasing the specificity of this assay.[11, 24] Thus far, the identification of clonality in pseudolymphoma lesions has not been predictive of lymphomatous transformation.[4, 17, 24]

Immunoglobulin light-chain analysis

Some subsets of B-cell lymphoma exhibit a monoclonal restriction to either kappa or lambda light chains. Because B-cell pseudolymphomas tend to be polyclonal, detection of such a light-chain clone by immunohistochemistry favors true B-cell lymphoma.[6]

Biopsy

Biopsy is necessary to establish a diagnosis of pseudolymphoma. An adequate sample extending well into the subcutis with avoidance of crush artifact is essential.

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Histologic Findings

Pseudolymphoma can be extremely difficult to differentiate from lymphoma on histologic grounds alone. For example, lymphocytoma cutis, a variant of pseudolymphoma with formation of B-cell germinal centers, is difficult to differentiate from follicular center lymphoma histologically. Histologically, the infiltrate simulates B-cell lymphoma and shows a nodular inflammatory infiltrate in the dermis. An infiltrate containing well-formed germinal centers limited to the papillary and upper reticular dermis (top-heavy) favors pseudolymphoma,[4] although much more overlap exists between true cutaneous lymphoma (especially marginal zone type) and drug-induced cutaneous lymphoid hyperplasia.[18]

The key histologic features that favor pseudolymphoma over lymphoma include the presence of a mixed infiltrate that includes histiocytes, eosinophils, and plasma cells, in addition to lymphocytes.[25] The presence of tingible body macrophages, preserved and evenly spaced follicular dendritic cells (highlighted by CD21 immunohistochemical staining), preserved polarized germinal centers, and lack of BCL-2 staining favor pseudolymphoma, but clinical correlation and follow up is required for definitive diagnosis.[3]

See the images below.

Biopsy specimens of pseudolymphoma vary substantia Biopsy specimens of pseudolymphoma vary substantially, but they most often exhibit a mixed inflammatory infiltrate with prominent lymphoid follicle formation.
A mixed inflammatory infiltrate with germinal cent A mixed inflammatory infiltrate with germinal centers is indicative of lymphocytoma cutis.

Drug-induced pseudolymphoma most often resembles the bandlike T-cell infiltrate of mycosis fungoides (MF).[4, 5] Some cases show a T-cell histologic pattern with a bandlike infiltrate in the papillary dermis, predominantly of small lymphocytes, with variable epidermotropism. Epidermotropism, if present, is mild and generally lacks Pautrier microabscesses. Deep perivascular and periadnexal infiltrates may be observed. Dermal edema, acanthosis, and spongiosis may help to differentiate this condition from true CTCL. While similar in overall appearance, CTCL typically displays conspicuous epidermotropism and papillary dermal fibroplasia and exhibits minimal spongiosis. Close inspection of the lymphocytes to identify cerebriform cells is important because the predominance of these atypical cells in the epidermis favors MF. Although these features mimic MF, the clinical presentation is often characteristic.[9]

Additionally, MF has a CD3+ CD4+ CD7- immunophenotype. Most drug-induced pseudolymphomas also contain CD3+ CD4+ T cells; however, CD7 is often retained. Because CD7 is lost in some pseudolymphomas and because it is not universally absent in CTCL, the CD3+ CD4+ CD7+ phenotype is not 100% specific for pseudolymphoma.[9, 8, 11] Loss of CD5 and restriction of the epidermotropic cells to a CD4 phenotype favors MF.

In nodular drug-induced T-cell pseudolymphoma, nodular T-cell infiltrates may be either isolated or may appear concomitantly with MF-like lesions. They consist of small lymphocytes admixed with variable histiocytes, plasma cells, and eosinophils. Nuclear atypia, when present, is generally mild.[4]

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Contributor Information and Disclosures
Author

Christine J Ko, MD Associate Professor, Departments of Dermatology and Pathology, Yale University School of Medicine

Christine J Ko, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, International Society of Dermatopathology

Disclosure: Nothing to disclose.

Coauthor(s)

Earl J Glusac, MD Professor, Departments of Pathology and Dermatology, Yale University School of Medicine

Earl J Glusac, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jon H Meyerle, MD Assistant Professor, Department Dermatology, Uniformed Services University of the Health Sciences; Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine; Chief, Immunodermatology, Walter Reed National Military Medical Center

Jon H Meyerle, MD is a member of the following medical societies: American Academy of Dermatology, Sigma Xi

Disclosure: Nothing to disclose.

Inbal Braunstein, MD Assistant Professor, Department of Dermatology, Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Acknowledgements

Donald Belsito, MD Professor of Clinical Dermatology, Department of Dermatology, Columbia University Medical Center

Donald Belsito, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, Dermatology Foundation, New York County Medical Society, New York Dermatological Society, Noah Worcester Dermatological Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Inbal Braunstein University of Pennsylvania School of Medicine

Disclosure: Nothing to disclose.

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.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jacqueline M Junkins-Hopkins, MD Associate Professor, Director, Division of Dermatopathology and Oral Pathology, Department of Dermatology, Johns Hopkins Medical Institutions

Jacqueline M Junkins-Hopkins, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and American Society of Dermatopathology

Disclosure: Nothing to disclose.

Michael S Lehrer, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Michael S Lehrer, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, and American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

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.

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.

References
  1. Brodell RT, Santa Cruz DJ. Cutaneous pseudolymphomas. Dermatol Clin. 1985 Oct. 3(4):719-34. [Medline].

  2. Choi TS, Doh KS, Kim SH, Jang MS, Suh KS, Kim ST. Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome. Br J Dermatol. 2003 Apr. 148(4):730-6. [Medline].

  3. Bergman R. Pseudolymphoma and cutaneous lymphoma: facts and controversies. Clin Dermatol. 2010 Sep-Oct. 28(5):568-74. [Medline].

  4. Albrecht J, Fine LA, Piette W. Drug-associated lymphoma and pseudolymphoma: recognition and management. Dermatol Clin. 2007 Apr. 25(2):233-44, vii. [Medline].

  5. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg. 1996 Dec. 15(4):250-7. [Medline].

  6. Callot V, Roujeau JC, Bagot M, Wechsler J, Chosidow O, Souteyrand P, et al. Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities. Arch Dermatol. 1996 Nov. 132(11):1315-21. [Medline].

  7. Maubec E, Pinquier L, Viguier M, et al. Vaccination-induced cutaneous pseudolymphoma. J Am Acad Dermatol. 2005 Apr. 52(4):623-9. [Medline].

  8. Magro CM, Crowson AN, Kovatich AJ, Burns F. Drug-induced reversible lymphoid dyscrasia: a clonal lymphomatoid dermatitis of memory and activated T cells. Hum Pathol. 2003 Feb. 34(2):119-29. [Medline].

  9. Ploysangam T, Breneman DL, Mutasim DF. Cutaneous pseudolymphomas. J Am Acad Dermatol. 1998 Jun. 38(6 Pt 1):877-95; quiz 896-7. [Medline].

  10. Magro CM, Crowson AN. Drug-induced immune dysregulation as a cause of atypical cutaneous lymphoid infiltrates: a hypothesis. Hum Pathol. 1996 Feb. 27(2):125-32. [Medline].

  11. Cerroni L, Kerl H. Diagnostic immunohistology: cutaneous lymphomas and pseudolymphomas. Semin Cutan Med Surg. 1999 Mar. 18(1):64-70. [Medline].

  12. Kazandjieva J, Tsankov N. Tattoos: dermatological complications. Clin Dermatol. 2007 Jul-Aug. 25(4):375-82. [Medline].

  13. Porto DA, Comfere NI, Myers LM, Abbott JJ. Pseudolymphomatous reaction to varicella zoster virus vaccination: role of viral in situ hybridization. J Cutan Pathol. 2009 Nov 4. [Medline].

  14. Michaels B, Michaels J, Mobini N. Prominent lymphoid infiltrate with a pseudolymphoma-like morphology: a new histological finding of injectable liquid silicone. J Cutan Pathol. 2009 Nov. 36(11):1224-6. [Medline].

  15. Camilot D, Arnez ZM, Luzar B, Pizem J, Zgavec B, Falconieri G. Cutaneous pseudolymphoma following tattoo application: report of two new cases of a potential lymphoma mimicker. Int J Surg Pathol. 2012 Jun. 20(3):311-5. [Medline].

  16. Altamura D, Calonje E, Liau Jl, Rogers M, Verdolini R. Diffuse cutaneous pseudolymphoma due to therapy with medicinal leeches. JAMA Dermatol. 2014 Jul. 150(7):783-4. [Medline].

  17. Bouloc A, Delfau-Larue MH, Lenormand B, Meunier F, Wechsler J, Thomine E, et al. Polymerase chain reaction analysis of immunoglobulin gene rearrangement in cutaneous lymphoid hyperplasias. French Study Group for Cutaneous Lymphomas. Arch Dermatol. 1999 Feb. 135(2):168-72. [Medline].

  18. Baldassano MF, Bailey EM, Ferry JA, Harris NL, Duncan LM. Cutaneous lymphoid hyperplasia and cutaneous marginal zone lymphoma: comparison of morphologic and immunophenotypic features. Am J Surg Pathol. 1999 Jan. 23(1):88-96. [Medline].

  19. Kitagawa KH, Grassi M. Zoledronic acid-induced cutaneous B-cell pseudolymphoma. J Am Acad Dermatol. 2011 Dec. 65(6):1238-40. [Medline].

  20. Addeo R, Montella L, Baldi A, Cennamo G, Guarrasi R, Faiola V, et al. Atypical cutaneous lymphoid hyperplasia induced by chemotherapy in a patient with advanced colon carcinoma. Clin Colorectal Cancer. 2007 Nov. 6(10):728-30. [Medline].

  21. Welsh JP, Ko C, Hsu WT. Lymphomatoid drug reaction secondary to methylphenidate hydrochloride. Cutis. 2008 Jan. 81(1):61-4. [Medline].

  22. Braun RP, French LE, Feldmann R, Chavaz P, Saurat JH. Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual cause of symmetrical upper eyelid nodules. Br J Dermatol. 2000 Aug. 143(2):411-4. [Medline].

  23. Goyal A, Moore JB, Gimbel D, Carter JB, Kroshinsky D, Ferry JA, et al. PD-1, S-100 and CD1a expression in pseudolymphomatous folliculitis, primary cutaneous marginal zone B-cell lymphoma (MALT lymphoma) and cutaneous lymphoid hyperplasia. J Cutan Pathol. 2015 Jan. 42 (1):6-15. [Medline].

  24. Bachelez H. The clinical use of molecular analysis of clonality in cutaneous lymphocytic infiltrates. Arch Dermatol. 1999 Feb. 135(2):200-2. [Medline].

  25. Burg G, Kerl H, Schmoeckel C. Differentiation between malignant B-cell lymphomas and pseudolymphomas of the skin. J Dermatol Surg Oncol. 1984 Apr. 10(4):271-5. [Medline].

  26. El-Dars LD, Statham BN, Blackford S, Williams N. Lymphocytoma cutis treated with topical tacrolimus. Clin Exp Dermatol. 2005 May. 30(3):305-7. [Medline].

  27. Baumgartner-Nielsen J, Lorentzen H. Imiquimod 5%: a successful treatment for pseudolymphoma. Acta Derm Venereol. 2014 Jul. 94(4):469. [Medline].

  28. Singletary HL, Selim MA, Olsen E. Subcutaneous interferon alfa for the treatment of cutaneous pseudolymphoma. Arch Dermatol. 2012 May. 148(5):572-4. [Medline].

  29. Tomar S, Stoll HL, Grassi MA, Cheney R. Treatment of cutaneous pseudolymphoma with interferon alfa-2b. J Am Acad Dermatol. 2009 Jan. 60(1):172-4. [Medline].

  30. Mikasa K, Watanabe D, Kondo C, Tamada Y, Matsumoto Y. Topical 5-aminolevulinic acid-based photodynamic therapy for the treatment of a patient with cutaneous pseudolymphoma. J Am Acad Dermatol. 2005 Nov. 53(5):911-2. [Medline].

  31. Lucinda TS, Hazel OH, Joyce LS, Hon CS. Successful Treatment of Tattoo-Induced Pseudolymphoma with Sequential Ablative Fractional Resurfacing Followed by Q-Switched Nd: YAG 532 nm Laser. J Cutan Aesthet Surg. 2013 Oct. 6(4):226-8. [Medline]. [Full Text].

 
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This localized example of pseudolymphoma shows an ill-defined, thin, erythematous plaque.
Pseudolymphomatous drug eruption due to captopril, marked by erythematous to purple papules, patches, and plaques.
This erythrodermic pseudolymphoma (T-cell pattern) typifies drug-induced pseudolymphoma, which is most often secondary to anticonvulsant therapy.
Biopsy specimens of pseudolymphoma vary substantially, but they most often exhibit a mixed inflammatory infiltrate with prominent lymphoid follicle formation.
This example of lymphocytoma cutis shows a localized, erythematous-to-brown, ill-defined plaque.
Lymphocytoma cutis of the shoulder, composed of flesh-colored or erythematous nodules in small groups.
This photograph of lymphocytoma cutis caused by an arthropod bite shows an erythematous scaling patch of the scalp with localized secondary alopecia.
A mixed inflammatory infiltrate with germinal centers is indicative of lymphocytoma cutis.
Well-developed lymphoid follicles in a background of mixed inflammatory cells with small lymphocytes are typical of lymphocytoma cutis.
 
 
 
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