Lymphomatoid Papulosis Reappraisal of Clinicopathologic Presentation and Classification Into Subtypes A, B, and C

STUDY Lymphomatoid Papulosis Reappraisal of Clinicopathologic Presentation and Classification Into Subtypes A, B, and C

Laila El Shabrawi-Caelen, MD; Helmut Kerl, MD; Lorenzo Cerroni, MD

Objectives: To analyze clinicopathologic features of lym- time, that some histopathologic patterns, ie, follicular mu- phomatoid papulosis and delineate the characteristics of cinosis (n=1), syringotropic infiltrates (n=1), epider- histopathologic variants (types A, B, and C). mal vesicle formation (n=2), and syringosquamous metaplasia (n=1), were associated with lymphomatoid Design: Retrospective nonrandomized study. papulosis. A distribution along hair follicles, or follicular lymphomatoid papulosis, was observed in 5 biopsy Setting: University-based dermatologic referral center. specimens. A bandlike rather than a wedge distribution of the infiltrate was seen in 5 specimens from patients Patients: Eighty-five patients with lymphomatoid papu- with lymphomatoid papulosis type A. Of 8 patients who losis. Clinical data and 1 or more biopsy specimens were had associated lymphoid malignancies, 4 had Hodgkin available for review in all cases. When possible, immu- disease and 4 had mycosis fungoides. nophenotypic and molecular analyses were carried out. Conclusions: Lymphomatoid papulosis is a cutaneous Results: Of these patients, 78 presented only 1 histo- disorder with multiple clinicopathologic features. Dif- pathologic subtype of lymphomatoid papulosis (64 had ferentiating between mycosis fungoides and anaplastic type A, 3 had type B, and 11 had type C). The last 7 pa- large cell lymphoma may be very difficult and some- tients presented more than 1 subtype (1 had A and B, 5 times impossible. In the spectrum of CD30+ cutaneous had A and C, and 1 had A, B, and C). Two patients had lymphoproliferative disorders, boundaries between these regional lymphomatoid papulosis, an unusual clinical pre- 2 entities are not clear-cut. sentation characterized by groups of lesions localized to 1 anatomic region. We observed, we believe for the first Arch Dermatol. 2004;140:441-447

HE CONCEPT OF DISORDERS liferative disorders such as mycosis fungoi- with a benign clinical course des (MF), anaplastic large cell lymphoma but a malignant appear- (ALCL), and Hodgkin disease (HD) has ance on histopathologic ex- been reported.4-6 Based on histopathologic amination is controversial. findings, 3 types, A, B, and C, differing in Lymphomatoid papulosis (LYP), charac- cytological and architectural features, have T 7 terized by spontaneously resolving pap- been delineated. We present a retrospec- ules and nodules with strikingly atypical tive study of 85 patients with LYP to rede- lymphoid cells, belongs to these disorders fine the clinicopathologic subtypes and vari- and has been a mystery since its descrip- ants of this disease. tion by Macaulay in 1968.1 Previously be- lieved to be an inflammatory process, it is METHODS now regarded as an indolent cutaneous lymphoma and is listed as such in the current PATIENTS European Organization for Research and Treatment of Cancer and World Health Or- Eighty-five patients were identified from the ganization classifications.2,3 Clinical le- database of the Department of Dermatology of sions of LYP vary from papules and nod- the University of Graz as meeting the clinicopathologic criteria of LYP. A review of the clini- From the Department of ules to—less commonly—vesicles and cal data assessed the following parameters: sex, Dermatology, University of pustules, and while individual lesions usu- age at diagnosis, morphology and localization Graz, Graz, Austria. The ally resolve within weeks or months, the dis- of the lesions, disease status, and disease as- authors have no relevant ease may recur for decades. In a minority sociation with other lymphoproliferative dis- financial interest in this article. of cases, association with other lymphopro- orders.

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Association With Lymphoma, Before/After Onset

Type No. of Patients Sex, M/F Median Age, y Distribution, G/R ALCL HD MF A64* 41/23 47 62/2 0/0 2/0 2/1 B 3 3/0 35 3/0 0/0 0/0 0/0 C 11 3/8 38 11/0 0/0 1/0 1/0 Overlapping types 7 3/4 50 7/0 0/0 1/0 0/0

Abbreviations: ALCL, anaplastic large cell lymphoma; G, generalized; HD, Hodgkin disease; MF, mycosis fungoides; R, regional. *In 42 patients histopathologic specimens showed epidermotropism in the background of a typical type A lesion; similar cases have sometimes been referred to as “overlapping type A/B.” Epidermotropism was found also in 10 patients with histopathologic features of lymphomatoid papulosis type C.

CD4 and CD56) served as antigen unmasking. Positive preparations (of tonsil tissue) and negative preparations (with no primary antibody) were used as controls.

MOLECULAR STUDIES

Genotypic analysis of the T-cell receptor gamma (TCR-␥) chain gene via polymerase chain reaction (PCR) was performed in 18 cases following a method previously described.8 Two per- cent to 5% of total template DNA, isolated from formalin- fixed, paraffin-embedded, 5-µm-thick tissue sections, was amplified using consensus primers V␥11 (250nM), V␥101 (250nM), and J␥11 (500nM). The DNA was initially denatur- ated at 94°C for 10 minutes, and then amplified during 40 cycles of 60 seconds at 94°C, 40 cycles of 30 seconds at 50°C, and 40 cycles of 30 seconds at 72°C. The amplified PCR product was Figure 1. Regional lymphomatoid papulosis showing a crop of erythematous then run on a 3.5% Metaphor agarose gel (FMC BioProducts, papules confined to the middle part of the arm. Rockland, Me), stained with ethidium bromide, and viewed un- der ultraviolet light. A discrete band, compared with previously identified positive and negative controls, was indicative HISTOPATHOLOGIC STUDIES of rearrangement of the TCR-␥ chain gene. Hematoxylin-eosin–stained sections of formalin-fixed, paraffin-embedded tissue from the 85 patients were ana- RESULTS lyzed. Specimens of second skin biopsies were available for 34 patients. We classified cases into 3 groups according to The number of lesions ranged from a few to several hun- the following types: dreds. Although most of them did not exceed 1 cm, in a Type A, or histiocytic type, when specimens displayed dense few cases larger tumors were clinically reminiscent of mixed infiltrates characterized by large atypical lymphocytes ALCL. Spontaneous resolution occurred between a few and neutrophils, eosinophils, histiocytes, and small lympho- weeks and a few months. cytes. The large atypical cells did not form sheets or constitute more than 50% of the infiltrate. Type B, or lymphocytic type, when specimens displayed TYPE A a monomorphous infiltrate of small to medium-sized lymphocytes with cerebriform nuclei similar to those observed in MF. Clinical Findings This variant has also been referred to in the literature as the MF-like type of LYP. Sixty-four patients (75%) (41 men and 23 women; me- Type C, when specimens displayed cytologic features simi- dian age, 47 years; range, 4-84 years) showed features lar to those of type A, but the atypical lymphoid cells either of the histiocytic type of LYP (Table 1). Three patients formed sheets or large nodules or represented more than 50% were younger than 19 years, and we observed age peaks of the infiltrate, simulating ALCL. This type has been referred in the second and sixth decade of life. A self-limited clini- to as borderline LYP-ALCL. cal course of disease was found in 13 (43%) of 30 pa- IMMUNOHISTOCHEMISTRY tients with follow-up data, while 17 (57%) of these 30 patients had protracted disease with relapses of papules Immunohistochemical analysis was performed on formalin- and nodules. Thirty-four patients were lost to follow- fixed, paraffin-embedded tissue sections using the following an- up. Papulonodular lesions confined to a single ana- tibodies: CD4 (Novocastra, Newcastle-upon-Tyne, England; di- tomic region, typical of regional LYP, were found in 2 lution, 1:30); CD8 (Dako Corp, Glostrup, Denmark; dilution, patients (Figure 1). 1:25); CD30 (Dako; undiluted); CD56 (Novocastra; dilution 1:20); and T-cell intracellular antigen 1 (TIA-1) (Immuno- Association With Non-Hodgkin Lymphoma. Two pa- tech, Marseille, France; dilution, 1:50). Microwave heating with tients had a prior diagnosis of MF, with lesions of LYP citrate buffer (for CD8, CD30, and TIA-1) or EDTA buffer (for developing 9 months and 10 years after diagnosis, re-

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Infiltrate Admixed Epidermal Changes Pleomorphic Cells Infiltration No. of Sup/ Follicular Type Specimens Deep Bandlike Adnex Hyperplasia Epidermo BullousMucinosis M/L S/M Multi Eos Neut A 104 93 5 6 61 55* 1 1 104 15 41 70 86 B8440580008053 C2424001613* 10245141623

Abbreviations: Adnex, adnexotropic; Eos, eosinophils; Epidermo, epidemotropism; M/L, medium/large; Multi, multinucleated; Neut, neutrophils; S/M, small/medium; Sup/Deep, superficial and deep. *Overlapping features characteristic of so-called composite types A/B and B/C.

A B

Figure 2. Lymphomatoid papulosis type A showing wedge-shaped infiltrate (A) with characteristic large pleomorphic and anaplastic lymphocytes (B).

spectively. The first patient presented with a single plaque on the chest characteristic of a solitary variant of MF. This patient was in clinical remission for both diseases at the time of the study. The other one who had conventional MF was lost to follow-up. In 1 patient MF followed LYP after a period of 3 years. The patient was alive and well 9 years after diagnosis of LYP. Two patients with HD sub- sequently developed typical lesions of LYP. Both were lost to follow-up.

Histopathologic Findings. One hundred four specimens showed the characteristic histopathologic features of LYP type A (Table 2 and Figure 2). The infiltrate was wedge-shaped in 93 specimens. In the remaining specimens 2 different types could be dis- cerned: one showed adnexotropic infiltrates with atypical lymphocytes clustering around hair follicles (n=5) or around eccrine ducts (n=1) (Figure 3), and the other had the cytologic characteristics of LYP type A but fea- tured a bandlike rather than a wedge-shaped infiltrate (n=5) (Figure 4). Epidermal hyperplasia and epidermotropism of atypical lymphocytes were seen in 61 and 55 specimens, respectively. Small to medium-sized atypical lymphoid cells admixed to large pleomorphic lymphocytes were observed in 15 specimens. Multinucle- ated lymphocytes were found in 41 specimens. The atypical lymphoid infiltrate showed numerous mitotic figures in 41 specimens. The admixed infiltrate contained eosinophils and neutrophils in 70 and 86 specimens, re- Figure 3. Syringotropic lymphomatoid papulosis with atypical cells along an spectively. eccrine duct with syringotropism of scattered atypical lymphocytes.

Additional Observations. Unusual and as yet unrecog- infiltrates (n=1), intraepidermal vesicle formation nized reaction patterns in LYP included the presence of (n=1), and syringosquamous metaplasia (n=1). One follicular mucinosis (n=1) (Figure 5), syringotropic patient with eruptive keratoacanthomas and typical

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Figure 4. A, Plaque-type lymphomatoid papulosis showing patchy perivascular infiltrate in the superficial dermis with small perivascular aggregates of reactive lymphocytes in the mid-dermis. B, Clusters of atypical lymphocytes are confined to the superficial part of the infiltrate.

Histopathologic Findings. Eight specimens with characteristic features of LYP type B were available for histopathologic evaluation. The infiltrate was bandlike in 4 specimens. Four tissue sections displayed extension of the infiltrate into the deep reticular dermis, with a wedge- shaped configuration in 1 instance (Figure 6). Epider- mal hyperplasia was found in 5 specimens. Epidermo- tropism of atypical lymphocytes was evident in all specimens (n=8). Atypical lymphocytes were small to medium-sized in all instances (n=8) and mitoses were rarely found. Five tissue sections revealed admixed eosinophils and 3 showed admixed neutrophils.

Phenotype. CD30 immunostaining revealed atypical lymphocytes in 3 of 5 tissue sections. Two specimens were Figure 5. Lymphomatoid papulosis associated with follicular mucinosis and tested for CD4 and CD8 (1 tested positive for CD4, and showing folliculotropism of pleomorphic lymphocytes. the other tested negative for both markers). Labeling of CD56 was observed in 1 of 2 specimens, and 1 of 1 tissue section tested positive for TIA-1. Genotyping re- lesions of LYP type A developed collision lesions, in vealed monoclonality of the TCR-␥ chain gene in 1 of 4 which atypical CD30+ lymphocyte–infiltrated keratoac- specimens. anthomas were observed. TYPE C Phenotype. All specimens (n=68) tested for CD30 showed this antibody’s characteristically crisp cell membrane stain- Clinical Findings ing (Table 3). In 5 of 16 specimens most atypical lymphocytes expressed CD4, and in 6 of these 16 tissue sec- Characteristic findings of LYP type C were observed in tions atypical lymphoid cells showed predominant 11 patients (13%) (8 women and 3 men; median age, 38 reactivity for CD8. Negativity for CD4 and CD8 was ob- years; range, 7-68 years). served in 4 of the 16 specimens, and double positivity of these markers in 1 instance. Atypical lymphoid cells were Association With NHL. One patient with a prior diag- stained by CD56 in 9 of 22 specimens and by TIA-1 in nosis of MF developed lesions of LYP type C after an in- 15 of 21 specimens. Clonal rearrangement of the TCR-␥ terval of 10 years (Figure 7). Partial data about this pa- chain gene was detected in 4 of 12 specimens. tient were published previously.9 The patient died of systemic lymphoma 5 years after biopsy-proven LYP. TYPE B Hodgkin disease was diagnosed 5 years before the oc- currence of LYP type C in 1 patient. The current pa- Clinical Findings tient’s status is not known.

We identified 3 patients (4%) with LYP type B (all were Histopathologic Findings. We reviewed 24 specimens men; median age, 35 years; range, 29-54 years). Two of with typical features of LYP type C (Figure 8). The in- them still had waxing and waning lesions of LYP at the filtrate was both superficial and deep in 24 tissue sec- time of the study, while 1 patient was lost to follow-up; tions, of which 9 showed a wedge-shaped configura- none of these 3 patients had associated lymphomas. tion. Epidermal hyperplasia was found in 16 tissue

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Type CD4+ CD8+ CD4−/CD8− CD4+/CD8+ CD30 CD56 TIA-1 M-TCR␥ A 5/16 6/16 4/16 1/16 68/68 9/22 15/21 4/12 B 1/2 0/2 1/2 0/2 3/5 1/2 1/1 1/4 C 1/3 1/3 0/3 1/3 16/16 3/6 4/5 1/2

Abbreviation: M-TCR␥, monoclonal rearrangement of T-cell receptor ␥ chain gene.

A B

Figure 6. Lymphomatoid papulosis type B showing wedge-shaped infiltrate (A) with predominance of small- to medium-sized pleomorphic lymphocytes (B). Epidermotropic atypical lymphocytes simulate mycosis fungoides.

sections, and intraepidermal atypical lymphocytes in 13. We observed subepidermal vesicle formation in 1 instance. Small to medium-sized pleomorphic cells admixed to large atypical lymphocytes were found in 5 tissue sections, and multinucleated lymphocytes in 14. Twenty-nine tissue sections showed numerous mitotic figures. Eosinophils and neutrophils were found in 16 and 23 tissue sections, respectively. Phenotype. CD30 stained atypical lymphocytes in all instances (16/16) (Figure 8C). A CD4+ phenotype was observed in one third of specimens, a CD8+ in one third, and a positivity for both in one third. Atypical lymphocytes were Figure 7. Mycosis fungoides associated with lymphomatoid papulosis positive for CD56 in 3 of 6 tissue sections, while TIA-1 was (type C). Erythematous patches and small plaques of mycosis fungoides detected in 4 of 5. Molecular analysis showed monoclonal on the trunk and upper extremities. Note erythematous papules of rearrangement of the TCR ␥-chain gene in 1 of 2 specimens. lymphomatoid papulosis at both axillae.

OVERLAPPING TYPES tifying so far unrecognized reaction patterns. In agreement with a previous observation, the median age of Clinical Findings patients in our group was 44 years.10 Only 6% of pa- Seven patients (8%) (3 men and 4 women; median age, 50 tients (n=5) were younger than 19 years. We therefore years; range, 12-73 years) developed different types of LYP. did not identify as many children as anticipated, which The most common association was between LYP type A led us to the speculation that in some instances the on- and C (5 cases). One patient had LYP types A and B, and 1 set of disease predated diagnosis. The 3 histopathologic had lesions of histopathologic subtypes A, B, and C. subtypes of LYP, namely, A, B, and C, did not differ significantly concerning the age at onset of the disease. Association With NHL. One patient developed lesions One of the most vexing problems in the classifica- of LYP type C 11 years after the diagnosis of HD and sub- tion of LYP is the presence of different patterns—those that sequently presented with findings characteristic of LYP have been defined types A, B, and C—and their differen- type A. The patient was in clinical remission for HD but tiation from other lymphomas such as MF and ALCL.11 Pa- still had waxing and waning lesions of LYP. tients diagnosed with LYP type A constituted by far the larg- est group in our study (75%). The wedge-shaped mixed- COMMENT cell infiltrate with variable numbers of large, atypical lymphocytes is readily recognizable, unless very early or We reviewed the clinicopathologic spectrum of LYP, shed- late stages are encountered. Although LYP type B has been ding new light on the histopathologic variants and iden- defined as “MF-like LYP,” histopathologic appearances over-

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Figure 8. Lymphomatoid papulosis, type C. A and B, Sheets of large anaplastic lymphocytes evocative of the histopathologic appearance of anaplastic large cell lymphoma. C, Staining for CD30 shows positive atypical cells in sheets.

lapping with other types of LYP were observed. In fact, a gress, a phenomenon that accounted for the term regress- bandlike rather than wedge-shaped infiltrate of atypical lym- ing atypical histiocytosis in the earlier literature.18 Results phoid cells was detected in 5% of type A lesions. More- from a large study on CD30+ lymphoproliferative disor- over, epidermotropism of pleomorphic lymphoid cells, a ders indicate that even the biological differences between cardinal feature of LYP type B, was evident in more than LYP and ALCL limited to skin cells is less pronounced than half of type A and C cases. These cases have also been re- expected, because in cases treated with chemotherapy referred to as composite type A/B, or type B/C LYP. Our ex- lapses of skin lesions can occur regardless of the original perience was that LYP type B should not be diagnosed un- classification.10 Taken together, LYP and ALCL only rep- less a combination of characteristic cytologic as well as resent 2 ends of a spectrum, and it has to be recognized architectural features is found. Architectural features on their that there is a small group of patients who do not fit neatly own do not suffice for a diagnosis of LYP type B. It is cru- in either of these categories. It seems likely that the spec- cial to stress that differentiation of LYP type B from MF can trum of CD30+ cutaneous lymphoproliferative disorders, only be achieved by clinicopathologic correlation, and that including LYP and ALCL, does not present clear-cut bound- a diagnosis of LYP type B should never be established with- aries between these 2 entities.19 out complete clinical information. Immunohistochemical Beside ALCL, there is a well-documented associa- analysis with CD30 may not be helpful in distinguishing tion of LYP with other lymphoproliferative disorders, es- these disorders, especially if one considers reports of CD30- pecially MF and HD.4-6 In concurrence with other obser- negative LYP type B.12,13 Such cases, however, should be vations, 9% of patients in our study had associated carefully interpreted, because a papular variant of MF shows lymphoproliferative neoplasms.2,20,21 However, the per- virtually identical histopathologic features. In our study, centage may be higher because long-term follow-up was in agreement with other reports, we found CD30-positive not always available. It is important to differentiate asso- intraepidermal lymphocytes in more than half of LYP type ciated lymphomas preceding or following LYP, especially B cases.14,15 Although it might be difficult to accept the con- if one deals with MF. If there is a history of MF before the cept of a type of LYP devoid of large atypical lymphocytes— development of CD30+ cutaneous lymphoid infiltrates, the hallmark of the disease described by Macaulay1—a par- transformation of MF to a CD30+ large cell lymphoma has allel with ALCL can be drawn. Even if large, anaplastic to be considered. Unlike the favorable prognosis of LYP and lymphoid cells are the rule in ALCL, in some cases the neo- primary cutaneous ALCL, transformed MF is usually as- plastic infiltrate may harbor a predominance of small to me- sociated with an aggressive clinical course. Differentia- dium lymphocytes, leading to the term “small-cell vari- tion of transformed MF from MF-associated LYP there- ant” of ALCL.16 Thus, it seems likely that the size of the fore carries profound clinical implications. Lesions with a cells alone is not sufficient to classify diseases of CD30+ lym- LYP-like morphology following MF, therefore, should be phoproliferative disorders. In this context, it should be men- interpreted with caution, as in some instances they may rep- tioned that in 7 patients (8%) we detected different LYP resent a transformation of MF. This might be true also for types from different biopsy specimens, underlying once 1 of the patients in our study, who had MF and subse- more the overlapping histopathologic features of the sub- quently developed LYP type C, and who eventually died types of LYP. Moreover, this percentage may be larger, as of systemic lymphoma. Unfortunately, data on molecular not all patients had multiple or repeated skin biopsies. analysis of the MF and LYP lesions in this patient were not Concerning LYP type C, the diagnosis is not always available, and we could not search for an identical clone, straightforward because of its close histopathologic re- as has been described in the literature.22-24 semblance to ALCL. The differential diagnosis between LYP An unusual clinical presentation in our study was the and primary cutaneous ALCL, even from a clinical stand- observation of clusters of lesions localized to a single ana- point, may be extremely difficult, if not impossible.17 Pri- tomic region in 2 patients. These cases of regional LYP are mary cutaneous ALCL usually presents with a single nod- more often found in children than in adults.25,26 During the ule or tumor, but satellites in the vicinity of a larger nodule course of the disease dissemination of lesions to other body are occasionally found and may simulate the clinical pic- sites may occur, a feature that was not observed in our pa- ture of localized LYP. In addition, patients with ALCL may tients.25 We would also like to underline some unusual and present with a widespread papular eruption rather than yet never reported histopathologic features, including the with a solitary lesion.10 Just as in LYP, lesions of primary presence of a syringotropic—rather than pilotropic— cutaneous ALCL have the capacity to spontaneously re- infiltrate, which was reminiscent of reaction patterns found

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 in cutaneous T-cell lymphomas such as MF. It is intrigu- 8. McCarthy KP, Sloane JP, Kabarowski JH, Matutes E, Wiedemann LM. A simpli- fied method of detection of clonal rearrangements of the T-cell receptor-gamma ing that we observed 3 additional reaction patterns well chain gene. Diagn Mol Pathol. 1992;1:173-179. documented in MF, such as follicular mucinosis, intrae- 9. Wolf P, Cerroni L, Smolle J, Kerl H. PUVA-induced lymphomatoid papulosis in a pidermal and subepidermal vesicle formation, and syrin- patient with mycosis fungoides. J Am Acad Dermatol. 1991;25:422-426. 10. Bekkenk MW, Geelen FA, van Voorst, et al. Primary and secondary cutaneous gosquamous metaplasia, probably reflecting the close re- CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lym- lationship between these 2 lymphoproliferative disorders. phoma Group on the long-term follow-up data of 219 patients and guidelines From an immunohistochemical standpoint, results with for diagnosis and treatment. Blood. 2000;95:3653-3661. 11. Willemze R, Meyer CJ, Van Vloten WA, Scheffer E. The clinical and histological CD56, being controversial in the literature, were interest- spectrum of lymphomatoid papulosis. Br J Dermatol. 1982;107:131-144. ing.27,28 We observed positivity in almost half of the le- 12. Whittaker S, Smith N, Jones RR, Luzzatto L. Analysis of beta, gamma, and delta T-cell receptor genes in lymphomatoid papulosis: cellular basis of two distinct sions irrespective of the histopathologic subtype. The fre- histologic subsets. J Invest Dermatol. 1991;96:786-791. quency of CD56 expression differs also significantly in 13. Tomaszewski MM, Lupton GP, Krishnan J, May DL. A comparison of clinical, various publications on ALCL and some of the difference morphological and immunohistochemical features of lymphomatoid papulosis 29 and primary cutaneous CD30(Ki-1)- positive anaplastic large cell lymphoma. might be attributable to the use of different antibodies. J Cutan Pathol. 1995;22:310-318. Expression of TIA-1, similar to previous observations, 14. Ralfkiaer E, Stein H, Wantzin GL, Thomsen K, Ralfkiaer N, Mason DY. Lympho- ranged between 70% (type A) to 80% (type C).30,31 Clini- matoid papulosis: characterization of skin infiltrates by monoclonal antibodies. Am J Clin Pathol. 1985;84:587-593. cally, cases with and without a cytotoxic phenotype did not 15. Agnarsson BA, Kadin ME. Host response in lymphomatoid papulosis. Hum Pathol. behave differently. Although CD4 and CD8 expression was 1989;20:747-752. observed in nearly equal proportions (5 of 16 cases vs 6 of 16. Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME. A small- cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. Am J Surg 16 cases), we believe that the overall number of cases tested Pathol. 1993;17:859-868. was too small to draw any conclusion. In fact, data from 17. LeBoit PE. Hodgkin’s disease, anaplastic large cell lymphoma, and lymphoma- the literature show that most LYP cases reveal a T-helper toid papulosis: another scalpel blunted. Am J Clin Pathol. 1995;104:3-4. 31-33 18. Flynn KJ, Dehner LP, Gajl-Peczalska KJ, Dahl MV, Ramsay N, Wang N. Regress- phenotype. ing atypical histiocytosis: benign or malignant? Minn Med. 1982;65:73-76. It was also interesting to observe the coexistence of 19. Drews R, Samel A, Kadin ME. Lymphomatoid papulosis and anaplastic large cell lymphomas of the skin. Semin Cutan Med Surg. 2000;19:109-117. eruptive keratoacanthomas and LYP type A in 1 of our pa- 20. Kadin ME, Vonderheid EC, Sako D, Clayton LK, Olbricht S. Clonal composition tients, a phenomenon previously described in the litera- of T cells in lymphomatoid papulosis. Am J Pathol. 1987;126:13-17. ture.34 Pseudoepitheliomatous epidermal hyperplasia simu- 21. Sanchez NP, Pittelkow MR, Muller SA, Banks PM, Winkelmann RK. The clinicopathologic spectrum of lymphomatoid papulosis: study of 31 cases. JAmAcad lating squamous cell carcinoma and known to occur in cases Dermatol. 1983;8:81-94. of LYP was excluded by standard histopathologic crite- 22. Davis TH, Morton CC, Miller-Cassman R, Balk SP, Kadin ME. Hodgkin’s disease, ria.35 This observation reflects the increased risk of devel- lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a com- 36 mon T-cell clone. N Engl J Med. 1992;326:1115-1122. oping nonlymphoid malignancies in LYP. 23. Wood GS, Crooks CF, Uluer AZ. Lymphomatoid papulosis and associated cuta- Our study showed in greater detail the wide clini- neous lymphoproliferative disorders exhibit a common clonal origin. J Invest Der- copathologic spectrum of LYP. It must be stressed once matol. 1995;105:51-55. 24. Chott A, Vonderheid EC, Olbricht S, Miao NN, Balk SP, Kadin ME. The dominant more that the diagnosis of LYP and its differentiation from T cell clone is present in multiple regressing skin lesions and associated T cell other lymphomas can only be achieved by synthesis of lymphomas of patients with lymphomatoid papulosis. J Invest Dermatol. 1996; 106:696-700. the clinical presentation, together with histologic and ge- 25. Scarisbrick JJ, Evans AV, Woolford AJ, Black MM, Russell-Jones R. Regional notypic features. lymphomatoid papulosis: a report of four cases. Br J Dermatol. 1999;141:1125- 1128. 26. Thomas GJ, Conejo-Mir JS, Ruiz AP, Linares Barrios M, Navarrete M. 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