Related Terms and Key Words: CD30+ lymphoma, eccrinotropic, granulomatous, lymphomatoid papulosis, methotrexate, lymphedema, papulonodular skin eruption, Primary cutaneous CD30 + lymphoproliferative disorder, Cutaneous T-cell lymphoma, Proliferative T-cell disorder, WHO/EORTC classification, chemokines, chemokine receptors
A chronic skin disease that presents with characterists of malignant T-cell lymphoma. However, it is important to remember that lymphotoid papulosis (LyP) is not classified as a true lymphoma. Also, it does not spread and is not fatal. It is therefore described as histologically malignant, but clinically benign. (1)
It is classified as a lymphoproliferative disorder. These account for about 25% of cutaneous T-cell lymphomas. The condition occurs equally between men and women and usually occurs in the fifth decade. Clinically, black people appear to have the disease much less frequently then other races.
The term lymphomatoid papulosis originally was used by Macaulay in 1968 to describe “a self-healing rhythmical paradoxical eruption, histologically malignant but clinically benign.” Due to the typical waxing and waning clinical course, lymphomatoid papulosis was previously considered a pseuodolymphomatous inflammatory process. However, the classification system for cutaneous lymphomas has evolved rapidly, and, during consensus meetings in 2003-2004, the World Health Organization—European Organization for Research and Treatment of Cancer (WHO-EORTC) classification grouped lymphomatoid papulosis among the indolent cutaneous T-cell lymphomas. (2)
LyP is divided into three subtypes, they include:
Type A - characterized by large 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. (2)
Uncommonly, patients may have more than one histologic subtype of lymphomatoid papulosis or other recently described associated histologic patterns.
Unknown at the present time and there is debate on whether or not it may be genetically caused. Several genetic defect have been identified in LyP lesions, but the specific cause has not been identified.
A few investigators have also discovered viruslike particles in lymphomatoid papulosis lesions examined under electron microscopy.
Signs and Symptoms:
Lymphomatoid papulosis appears as recurrent small, raise skin lesions. The color ranges from red to brown in color. The most commonly occur on the trunk, arms, and legs in crops but may also occur on the palms, soles, face, and scalp. Very rarely, LyP lesions may be present in the mouth and throat. The lesions heal spontaneously within several weeks and leave a small, hypopigmented scar.
Done by skin biopsy. This is critical as the lesions may appear as the same for numerous other skin nodular growths.
Biopsies are also critical to rule out mycoses fungoides, cutaneous anaplastic large cell lymphoma, cutaneous Hodgkin’s disease, cutaneous leukemia, scabies, insect bites, and drug reactions.
If after biopsy the result come back other then lymphotoid papulosis, then the treating physician will order other types of tests to establish a correct diagnosis.
Cutaneous CD30+ (Ki-1) Anaplastic Large-Cell Lymphoma, Cutaneous T-Cell Lymphoma, Folliculitis, Insect Bites, Langerhans Cell Histiocytosis, Leukemia Cutis, Lymphocytoma Cutis, Milia, Miliaria, Scabies
The disease itself is not fatal. However, 10 to 20% of patients will also develop an associated systemic lymphoma, typically anaplastic large cell, Hodgkinís disease, or mycoses fungoides.
If any type of secondary malignancy develops, then that would alter the outlook, depending on the type of malignancy.
Patients may choose not to treat the lesions and they usually heal spontaneously over 1-2 months.
Historically, treatment for the skin lesions themselves has been corticosteroid creams or ointment. Another option that can lead to faster healing is with low dose methotrexate. This is a type of chemotherapy that inhibits cell division. The one weak point in this treatment is that the lesions treated with methotrexate will generally return several weeks after therapy.
Another strong, aggressive treatment is oral psoralen plus ultraviolet light, so-called PUVA therapy.
Other treatments might include: carmustine, topical nitrogen mustard, topical MTX, topical imiquimod cream, intralesional interferon, low-dose cyclophosphamide, chlorambucil, medium-dose UVA-1 therapy, excimer laser therapy, photodynamic therapy, and dapsone help disease suppression.
Lymphomatoid papulosis has a chronic, indolent course in most patients.
However, associated lymphomas may arise with LyP. These include immunoblastic lymphoma, lethal midline granuloma (currently considered as natural killer cell lymphoma in many patients), and systemic lymphocytic lymphoma. In most patients, the malignancy develops many years after the diagnosis of lymphomatoid papulosis.
(1) Lymphomatoid Papulosis Know Cancer
(2) Lymphomatoid papulosis eMedicine/Medscape
Lymphomatoid papulosis: Clinical and pathological findings in 18 patients.
[Article in English, Spanish]
Fernández-Guarino M, Carrillo-Gijón R, Jaén-Olasolo P.
Servicio de Dermatología, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, España.
BACKGROUND: Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative skin disease that has been described in association with Hodgkin lymphoma. It has also been reported to progress to mycosis fungoides or cutaneous anaplastic large-cell lymphoma.
OBJECTIVE: To study the clinical and histologic features of LyP and response to treatment in a patient series.
MATERIALS AND METHODS: For this retrospective, descriptive, observational study of patients with histologically confirmed LyP and sufficient follow-up data on record, we extracted histologic findings on skin biopsy, clinical presentation, clinical course, and response to treatments.
RESULTS: Eighteen patients (10 male, 8 female) were identified. Most biopsies (14/18, 78%) showed a wedge-shaped lymphocytic infiltrate with CD30(+), CD3(+), and CD56(-) cells. A type A histologic pattern was present in the biopsies of 83% of the patients. The most common presentation (83%) consisted of papules on the trunk; for 62% LyP resolved after a single episode. Twelve percent of the patients developed mycosis fungoides (mean follow-up, 7 years); no other associations were noted.
DISCUSSION: Although few series of patients with LyP have been published in recent years, the findings reported generally coincide with our observations.
CONCLUSION: LyP is typically a CD30(+) lymphoproliferative disorder that usually runs a benign course and responds well to treatment.
Granulomatous and eccrinotropic lymphomatoid papulosis.
Jain N, Gutte R, Jadhav P, Khopkar U.
Department of Dermatology, Seth G.S. Medical College and King Edward Memorial Hospital, Mumbai, India.
Keywords: CD30+ lymphoma, eccrinotropic, granulomatous, lymphomatoid papulosis, methotrexate
Lymphomatoid papulosis has been classically described as a chronic, recurrent and self-healing papulonecrotic or papulonodular skin eruption, which is clinically benign and histopathologically malignant. The histologic characteristics of lymphomatoid papulosis are suggestive of a cluster of differentiation 30+ (CD30+) malignant lymphoma, and it is best regarded as a low grade cutaneous T cell lymphoma (CTCL). We hereby report a case of granulomatous and eccrinotropic lymphomatoid papulosis in a 40- year-old male. There was no systemic involvement. The patient was treated with low dose oral methotrexate with good response.
Lymphomatoid papulosis in children: experience of five cases and the treatment efficacy of methotrexate.
Yip L, Darling S, Orchard D.
Department of Dermatology, The Royal Children's Hospital, Victoria, Australia. firstname.lastname@example.org
Keywords: CD30;lymphomatoid papulosis; methotrexate
We present a case series of childhood lymphomatoid papulosis (LyP), an entity which is commonly misdiagnosed and poorly described in the paediatric dermatology literature. Clinically and histologically, the features of LyP in children can mimic insect bite reactions, with prominent dermal neutrophils and eosinophils. However, CD30 immunohistochemical staining of atypical lymphocytes within a mixed inflammatory infiltrate should point to the diagnosis of LyP. There is no consensus to guide management of childhood LyP due to its rarity and largely unknown natural course. We discuss our experience with LyP in five children and the use of methotrexate to induce rapid resolution of persistent lesions and to reduce recurrences in two children. Although none of our cases have experienced malignant transformation to date, life-long monitoring is advocated.
In search of prognostic indicators for lymphomatoid papulosis: A retrospective study of 123 patients. Oct 2011
de Souza A, El-Azhary RA, Camilleri MJ, Wada DA, Appert DL, Gibson LE.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota.
Key words: CD30 lymphoproliferative disorder; chemokines and chemokine receptors; cutaneous lymphomas; lymphomatoid papulosis; T-cell gene rearrangement
BACKGROUND: Lymphomatoid papulosis (LyP) is a benign recurrent papulonodular skin eruption with histologically malignant features that sometimes (10%-20%) progresses to lymphoma.
OBJECTIVE: We retrospectively evaluated the clinical course of patients with LyP and identify prognostic factors possibly indicating a malignant course.
METHODS: Clinical, histopathologic, and immunologic features and molecular genetics were examined and correlated with clinical course and outcomes. Immunophenotyping and chemokine profiling were performed in select skin biopsy samples. A follow-up questionnaire was sent to patients. Clinical course and association with neoplastic disorders were correlated with LyP subtypes, molecular genetics, and immunophenotyping studies.
RESULTS: Of 123 patients with LyP (1991-2008) followed up a mean of 4 years (range, 2 months to 14 years), 17 (14%) had an associated hematologic malignancy, 8 of which were mycosis fungoides. Histopathologic analyses demonstrated classic LyP type A (n = 69), B (n = 13), or C (n = 6), and a slight predominance of T-cell CD8 marker expression for type A. More than one type of lesion was present in 9 patients with a higher incidence of hematologic malignancies. T-cell receptor gene rearrangement positivity was about two times higher, with LyP associated with hematologic malignancy (82% vs 44%; odds ratio 5.7; P = .02). Chemokine studies in a subset of 25 patients showed chemokine receptor (CCR) CCR4(+) and thymus and activation-related chemokine (TARC(+)) in all LyP types and CCR3(+) and chemokine-related receptor (CXCR) CXCR3(+) in types B and C.
LIMITATIONS: Retrospective study design is a limitation.
CONCLUSIONS: Positive T-cell receptor gene rearrangement or diagnosis of mixed-type LyP may be a prognostic indicator of disease more prone to progress to lymphoma.
EORTC, ISCL, and USCLC consensus recommendations for the treatment of primary cutaneous CD30-positive lymphoproliferative disorders: lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma.
Kempf W, Pfaltz K, Vermeer MH, Cozzio A, Ortiz-Romero PL, Bagot M, Olsen E, Kim YH, Dummer R, Pimpinelli N, Whittaker S, Hodak E, Cerroni L, Berti E, Horwitz S, Prince HM, Guitart J, Estrach T, Sanches JA, Duvic M, Ranki A, Dreno B, Ostheeren-Michaelis S, Knobler R, Wood G, Willemze R.
Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. email@example.com
Primary cutaneous CD30(+) lymphoproliferative disorders (CD30(+) LPDs) are the second most common form of cutaneous T-cell lymphomas and include lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma. Despite the anaplastic cytomorphology of tumor cells that suggest an aggressive course, CD30(+) LPDs are characterized by an excellent prognosis. Although a broad spectrum of therapeutic strategies has been reported, these have been limited mostly to small retrospective cohort series or case reports, and only very few prospective controlled or multicenter studies have been performed, which results in a low level of evidence for most therapies. The response rates to treatment, recurrence rates, and outcome have not been analyzed in a systematic review. Moreover, international guidelines for staging and treatment of CD30(+) LPDs have not yet been presented. Based on a literature analysis and discussions, recommendations were elaborated by a multidisciplinary expert panel of the Cutaneous Lymphoma Task Force of the European Organization for Research and Treatment of Cancer, the International Society for Cutaneous Lymphomas, and the United States Cutaneous Lymphoma Consortium. The recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30(+) LPDs.
Full Text article
Clonal T-cell receptor β-chain gene rearrangements in differential diagnosis of lymphomatoid papulosis from skin metastasis of nodal anaplastic large-cell lymphoma.
Akilov OE, Pillai RK, Grandinetti LM, Kant JA, Geskin L.
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
BACKGROUND: In patients with a history of nodal anaplastic large-cell lymphoma (ALCL), differentiation of type C lymphomatoid papulosis from cutaneous involvement of systemic ALCL may be challenging because the 2 entities may exhibit identical histologic features. Although metastatic ALCL generally carries the same clone as the primary lymphoma, expression of a distinct clone likely represents a distinct process.
OBSERVATIONS: A 54-year-old white man had a history of anaplastic lymphoma kinase 1-negative ALCL in the right inguinal lymph node 6 years ago. A complete response was achieved after 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone administered in 21-day cycles) and radiation therapy. After 3½ years, the patient observed waxing and waning papules and nodules. Examination of the biopsy specimen revealed a dense CD30(+) lymphocytic infiltrate; no evidence of systemic malignancy was evident on positron emission tomography. Although clinically the presentation was consistent with lymphomatoid papulosis, metastatic ALCL had to be excluded. Polymerase chain reaction analysis with T-cell receptor γ-chain gene rearrangement (TCR-γR) was performed on the original lymph node and new skin lesions. Results of the TCR-γR analysis were positive for clonality in both lesions. However, separate clonal processes were identified. The identification of distinct clones supported the clinical impression of lymphomatoid papulosis.
CONCLUSION: Polymerase chain reaction analysis of TCR-γR is a useful method for distinguishing different clonal processes and is recommended when differentiation of primary and secondary lymphoproliferative disorders is required.
Author Affiliations: Department of Dermatology, University of Pittsburgh (Drs Akilov, Grandinetti, and Geskin), and Departments of Pathology (Drs Pillai and Kant) and Human Genetics (Dr Kant), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Lymphomatoid papulosis in children. Nov 1995
Lymphomatoid papulosis in a child Oct 1993
Disease DB 33778