STUDY The Clonal Nature of Pityriasis Lichenoides Jeffrey M. Weinberg, MD; Leonard Kristal, MD; Lillian Chooback, PhD; Paul J. Honig, MD; E. Michael Kramer, MD; Stuart R. Lessin, MD Background: Pityriasis lichenoides et varioliformis acuta PLC. These samples were analyzed by PCR/DGGE. (PLEVA) and pityriasis lichenoides chronica (PLC) are be- nign lymphocytic infiltrates of the skin that classically pre- Main Outcome Measure: The presence or absence sent as either a recurrent papulonecrotic eruption (PLEVA) of T-cell receptor gene rearrangements on PCR/DGGE or a persistent, scaling, papular eruption (PLC). Obser- analysis corresponding to a clonal population of T vations of both types of lesions present on individual pa- cells. tients have led to speculation that both entities are re- lated. Previous studies evaluating the DNA of biopsy Results: Of 14 PLEVA specimens, 8 (57%) demon- specimens from patients with PLEVA and PLC revealed strated monoclonal T-cell receptor gene rearrange- clonal T-cell receptor ␤ gene rearrangements. ments; 1 (8%) of 13 PLC specimens showed a gene re- arrangement (P=.008, Fisher exact test). Objective: To analyze and compare the T-cell popula- tions between lesions of PLEVA and PLC. Conclusions: Our results demonstrate the polyclonal na- ture of the lymphocytic infiltrate found in almost all of Design: Retrospective and prospective analysis of pa- the PLC specimens, which contrasts with the mono- tient tissue samples, classified by histologic analysis. Ex- clonal nature found in most of the PLEVA specimens. tracted DNA from 13 skin biopsy specimens with the di- These differences may represent different stages of the agnosis of PLC and 14 skin biopsy specimens with the clinical evolution of a single entity that results from vary- diagnosis of PLEVA was analyzed by polymerase chain ing host immune responses to pathogenic factors. Spe- reaction/denaturing gradient gel electrophoresis cifically, we propose that PLEVA is a benign clonal T- (PCR/DGGE). cell disorder in which the clone arises from a subset of T cells in lesions of PLC. The host immune response to this Setting: Molecular diagnostic laboratory at an aca- clone determines the clinical and histologic findings in demic medical center. PLEVA. Patients: Twenty-seven tissue samples were obtained from patients with a histologic diagnosis of PLEVA or Arch Dermatol. 2002;138:1063-1067 ITYRIASIS LICHENOIDES is char- (PLC). Brocq6 later included PLC in his acterized by papulosqua- classification of parapsoriasis as guttate mous to papulonecrotic le- parapsoriasis. In 1916, Mucha7 re- sional morphology, a chronic described the acute form of pityriasis li- and recurrent clinical course, chenoides, distinguishing it from both PLC and, as demonstrated by histopathologic and other diseases. This entity was termed From the Department of P Dermatology, University of analysis, a lichenoid infiltrate with vari- pityriasis lichenoides et varioliformis acuta 8 Pennsylvania (Drs Weinberg, able dermal hemorrhage and keratinocyte (PLEVA) by Habermann in 1925. Accord- Chooback, and Lessin), the necrosis. Pityriasis lichenoides and its prin- ingly, PLEVA is also known as Mucha- Children’s Hospital of cipal variants were identified and re- Habermann disease. Philadelphia (Drs Kristal and ported in a series of articles published in Honig), and Thomas Jefferson the late 19th and early 20th centuries.1 It For editorial comment Medical College (Dr Kramer), was first described by Neisser2 and Jadas- see page 1089 Philadelphia, Pa. Dr Weinberg sohn3 in separate reports in 1894; both in- is now with the Department cluded cases of what would now be con- Observations of both acute and of Dermatology, sidered acute and chronic variants of the chronic lesions present on the same indi- St Luke’s–Roosevelt Hospital 4 5 Center, New York, NY, disease. Juliusberg redescribed the chronic vidual have led to speculation that both and Dr Lessin is now with form of pityriasis lichenoides in 1899 and entities are related to and may be a part the Fox Chase Cancer Center, designated it as a separate entity, introduc- of a continuous disease spectrum.9 The Philadelphia. ing the term pityriasis lichenoides chronica term pityriasis lichenoides can be used to (REPRINTED) ARCH DERMATOL / VOL 138, AUG 2002 WWW.ARCHDERMATOL.COM 1063 ©2002 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 MATERIALS AND METHODS DNA from formalin-fixed paraffin-embedded blocks (21 ret- rospective cases) was extracted in the following manner. Ten PATIENT SAMPLES 10-mm sections were cut from each block, deparaffinized in xylene, rinsed with 95% ethanol, dried, resuspended in In the present study, 27 biopsy specimens were analyzed: tris-EDTA (10mM Tris–hydrochloric acid and 1mM EDTA, 13 from patients with PLC and 14 from patients with PLEVA. pH 7.8) and incubated with proteinase K (Sigma-Aldrich Of the 27 cases, 6 (4 PLC and 2 PLEVA) were analyzed pro- Corp, St Louis, Mo) at 37°C overnight. Samples were heated spectively, and 21 (9 PLC and 12 PLEVA) were studied ret- for 10 minutes at 95°C (inactivate proteinase K), spun, and rospectively from archived tissue specimens. Informed con- supernatants were phenol-chloroform extracted and etha- sent and approval by the institutional review board of the nol precipitated. Dried DNA was resuspended in sterile wa- University of Pennsylvania, Philadelphia, was obtained to ter and used for PCR. study unused portions of diagnostic samples. In the retro- spective arm of the study, questionnaires were mailed to the patients’ primary dermatologists to obtain the follow- PCR/DDGE ANALYSIS OF TCR␥ GENE ing information: patient age at biopsy, duration of erup- REARRANGEMENTS AND STATISTICAL ANALYSIS tion prior to biopsy, location of eruption, and follow-up. We used the method of Wood et al17 to perform PCR/ HISTOPATHOLOGIC ANALYSIS DGGE analysis of TCRγ gene rearrangements. Genomic ␥ All hematoxylin- eosin–stained skin biopsy specimens were DNA was PCR-amplified using 2 sets of TCR-V and ␥ reviewed by one of us (E.M.K.) in a blinded fashion to es- TCR-J consensus oligonucleotide primers (primers ␥ ␥ ␥ ␥ tablish uniform diagnosis. All 27 skin biopsy specimens in- V 1-8 and J 1-2; primers V 9 and J 1-2) in 2 separate cluded in this study were assigned a diagnosis of either PLEVA PCR reactions. To detect clonality, PCR products were or PLC. Histologic diagnosis was based on the following 4 analyzed by DGGE using a DGGE System (CBS Scientific criteria: (1) density of the lymphocytic infiltrate, (2) degree Company Inc, Del Mar, Calif) according to manufactur- ␥ of epidermal necrosis, (3) number of extravasated erythro- er’s specifications. Our detection sensitivity of TCR PCR/ 18 cytes, and (4) number of necrotic keratinocytes. DGGE analysis of skin biopsy specimens is at the 1% level and comparable with others reports.17 Two-by-two DNA EXTRACTION comparisons were made between cases of PLEVA and PLC with and without detection of T-cell clonality by the Genomic DNA was extracted from snap frozen samples Fisher exact test using StatView II software (Abacus Con- (6 prospective cases) as previously described.16 Genomic cepts Inc, Berkeley, Calif). encompass both acute and chronic presentations that are cell clonality in PLEVA using PCR of TCR gene rear- characterized by papulosquamous lesions located pri- rangements. An analysis of 13 of 20 PLEVA biopsy speci- marily on the trunk or extremities. The papules in PLEVA mens revealed the presence of a dominant T-cell clone. develop immediately and heal spontaneously with cen- Despite its lymphoproliferative nature, PLEVA is a clini- tral necrosis. The acute episodes are recurrent and per- cally benign entity with no significantly documented as- sistent. The maculopapular lesions of PLC develop less sociation with malignant lymphoma,9 except for a few, quickly with an adherent scale and resolves spontane- poorly documented case reports.14 ously with residual pigmentary changes. Both lesions his- Another recent study evaluated clonality in cases of tologically show similarities. The lesions of PLEVA re- PLC15: 6 cases of PLC were analyzed using a frozen sec- veal a superficial and deep perivascular lymphocytic tion–immunoperoxidase technique and PCR/ infiltrate accompanied by lymphocytes that obscure the denaturing gradient gel electrophoresis (PCR/DGGE). Of dermoepidermal interface, where there are also extrava- these, 3 demonstrated a monoclonal gene rearrange- sated erythrocytes and necrotic keratinocytes. The le- ment. The purpose of the present study was to analyze sions of PLC have a bandlike lymphocytic infiltrate with and compare the T-cell populations, by TCR gene rear- a few extravasated erythrocytes in the papillary dermis rangement analysis, in lesions of PLC and PLEVA in an and vacuoles and necrotic keratinocytes at the dermo- attempt to develop a model of the clonal relationship be- epidermal interface. tween the 2 disorders. To our knowledge, our study is The etiology of these disorders remains unknown. the first to directly compare both entities. Immunohistochemical analysis has found similarities in 10 both entities. Molecular characterization of the infil- RESULTS trating cells in a small series of patients with PLEVA in- dicated that the lymphocytic infiltrate is lymphoprolif- CLINICOPATHOLOGIC CORRELATION erative in nature11 and demonstrated a monoclonal population of T cells by Southern blot analysis of T-cell Of the 27 specimens analyzed, 13 were classified as PLC receptor(TCR) ␤ gene rearrangement. In addition, Pan- and 14 as PLEVA based on the histologic criteria outlined hans et al12 described the case of a 7-year-old boy with in the “Materials and Methods” section. Figure 1 illus- atypical CD30-positive cells and a clonal TCR gene re- trates the histologic findings of PLC: a sparse, superficial arrangement by polymerase chain reaction (PCR) of TCRγ perivascular lymphocytic infiltrate associated with a few genes. Recently, Dereure et al13 reported a study of T- extravasated erythrocytes in the papillary dermis and some (REPRINTED) ARCH DERMATOL / VOL 138, AUG 2002 WWW.ARCHDERMATOL.COM 1064 ©2002 American Medical Association.