Cases Of Lymphomatoid Papulosis Research Articles

Localized lymphomatoid papulosis: Unilesional lymphomatoid papulosis, regional lymphomatoid papulosis, and persistent agmination of lymphomatoid papulosis.

Lymphomatoid papulosis (LYP), the most common primary cutaneous CD30-positive lymphoproliferative disorder, is heralded by multiple papular and nodular lesions at anatomically discontiguous cutaneous sites. The histologic patterns are protean. An uncommon form of LYP is one that is anatomically confined. Cases of unilesional LYP, regional LYP, and persistent agmination of LYP were encountered in the routine and consultative practices of Weill Cornell Medicine, Division of Dermatopathology. The clinical presentation, outcomes, light microscopic findings, and phenotypic profile are reviewed. There were 10 cases of LYP presenting as solitary plaques or nodules primarily occurring in older patients and without a relevant medical history in most. Most cases occurred at an acral site with many localized to the foot; the morphology was one of a necrotizing angiocentric type E pattern and borderline type C morphology. Two of the unilesional patients in our series went on to develop mycosis fungoides, one at the initial site of unilesional type A LYP, and the other at a discontiguous site. Excluding one case, the solitary lesions underwent complete regression; after the lesions regressed, some cases had no apparent recurrence. The second anatomically confined variant of LYP in our series was regional LYP exhibiting a type E morphology in two cases and a hybrid type A and granulomatous eccrinotropic morphology in one case. There was no subsequent development of lymphoma, nor was there any spread to additional anatomic sites. The final category was persistent agmination of LYP, whereby the agminated papules of LYP were superimposed on a plaque of cutaneous T-cell lymphoma represented by mycosis fungoides in two and follicular helper T-cell lymphoma in one. In conclusion, anatomically confined LYP defines an uncommon form of LYP, but it is an important one to recognize because the histology can be worrisome despite an indolent clinical course. The clinical presentation, the infrequent association with lymphoma/leukemia, and histology are similar to conventional LYP, although there appears to be a greater tendency for complete regression without recurrence, excluding cases of persistent agmination of LYP whereby the clinical course warrants categorization as a form of cutaneous T cell lymphoma (CTCL).

Catalyst for catalytic oxidation of furfural for preparation of maleic acid, preparation method and use thereof

Lymphomatoid papulosis (LYP), the most common primary cutaneous CD30-positive lymphoproliferative disorder, is heralded by multiple papular and nodular lesions at anatomically discontiguous cutaneous sites. The histologic patterns are protean. An uncommon form of LYP is one that is anatomically confined. Cases of unilesional LYP, regional LYP, and persistent agmination of LYP were encountered in the routine and consultative practices of Weill Cornell Medicine, Division of Dermatopathology. The clinical presentation, outcomes, light microscopic findings, and phenotypic profile are reviewed. There were 10 cases of LYP presenting as solitary plaques or nodules primarily occurring in older patients and without a relevant medical history in most. Most cases occurred at an acral site with many localized to the foot; the morphology was one of a necrotizing angiocentric type E pattern and borderline type C morphology. Two of the unilesional patients in our series went on to develop mycosis fungoides, one at the initial site of unilesional type A LYP, and the other at a discontiguous site. Excluding one case, the solitary lesions underwent complete regression; after the lesions regressed, some cases had no apparent recurrence. The second anatomically confined variant of LYP in our series was regional LYP exhibiting a type E morphology in two cases and a hybrid type A and granulomatous eccrinotropic morphology in one case. There was no subsequent development of lymphoma, nor was there any spread to additional anatomic sites. The final category was persistent agmination of LYP, whereby the agminated papules of LYP were superimposed on a plaque of cutaneous T-cell lymphoma represented by mycosis fungoides in two and follicular helper T-cell lymphoma in one. In conclusion, anatomically confined LYP defines an uncommon form of LYP, but it is an important one to recognize because the histology can be worrisome despite an indolent clinical course. The clinical presentation, the infrequent association with lymphoma/leukemia, and histology are similar to conventional LYP, although there appears to be a greater tendency for complete regression without recurrence, excluding cases of persistent agmination of LYP whereby the clinical course warrants categorization as a form of cutaneous T cell lymphoma cutaneous T cell lymphoma (CTCL).

Genomic Analysis of Cutaneous CD30-Positive Lymphoproliferative Disorders

Primary cutaneous CD30+ T-cell lymphoproliferative disorders are the second most common cutaneous lymphomas. According to the World Health Organization, CD30+ T-cell lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. C-ALCL and LyP are thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms but share the same histology of medium to large CD30+ atypical lymphoid cell infiltrates. Because the behavior of these entities is different clinically and prognostically, we aim to search for oncogenic genomic variants using whole-exome sequencing that drive the development of LyP and C-ALCL. Clinical information, pathology, immunohistochemistry, and T-cell rearrangements on six cases of LyP and five cases of C-ALCL were reviewed to confirm the rendered diagnosis before whole-exome sequencing of all specimens. Both LyP and C-ALCL had recurrent alterations in epigenetic modifying genes affecting histone methylation and acetylation (SETD2, KMT2A, KMT2D, and CREBBP). However, they also harbor unique differences with mutations in signal transducer and activator of transcription gene STAT3 of the Jak/signal transducer and activator of transcription pathway and EOMES, a transcription factor involved in lymphocyte development, only noted in C-ALCL specimens. Genomic characterization of LyP and C-ALCL in this series confirms the role of multiple pathways involved in the biology and development of these lymphomatous processes. The identification of similar aberrations within the epigenetic modifying genes emphasizes common potential development mechanisms of lymphomagenesis within lymphoproliferative disorders being shared between LyP and C-ALCL; however, the presence of differences may account for the differences in clinical course.

Genomic Analysis of Cutaneous CD30-Positive Lymphoproliferative Disorders

Primary cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPD) are the second most common cutaneous lymphomas. According to the World Health Organization (WHO), CD30+ LPD include primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. pcALCL and LyP is thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms, but share the same histology of medium to large CD30+ atypical lymphoid cell infiltrates. Because the behavior of these entities is different clinically and prognostically, we aim to search for oncogenic genomic variants using whole exome sequencing (WES) that drive the development of LyP and pcALCL.Clinical information, pathology, immunohistochemistry, and T-cell rearrangements on six cases of LyP and five cases of pcALCL were reviewed to confirm the rendered diagnosis prior to WES of all specimens. All cases of CD30 LPD had recurrent mutations in at least one of the epigenetic modifying genes, with the most frequent mutations found in the mixed lineage methyltransferase family involved in the methylation of H3K4: CREBBP (27%), KMT2A (36%), KMT2D (36%), SETD2 (27%), and SMARCA4 (27%) (Figure). Within the JAK/STAT pathway, mutations of STAT3 were observed in 2 cases of pcALCL (n=2, 18%), STAT5B in one case of LyP (n=1, 9%) and JAK1 mutation in one case of LyP(n=1, 9%). Lastly, mutations were also identified in the T-cell signaling pathway. 3/5 cases of pcALCL demonstrated loss of function mutations in EOMES, a T-box transcription factor important in lymphocyte development. We had two cases of C-ALCL and one case of LyP with NOTCH1 mutations supporting the importance of this gene in T-cell lymphomas.TP53 mutations and copy number loss is more characteristic of aggressive lymphomas and these abnormalities were absent in pcALCL and LyP and may explain the indolent nature of CD30+ LPD.While the JAK/STAT pathway, T-signaling, and epigenetic alterations possibly play a role in the pathogenesis of these diseases, genes involved in cell-cycle control and apoptosis (ie. TP53) that are characteristic of more aggressive diseases were not identified. Extending this investigation to a larger number of samples will allow us to detect additional mutations that may help distinguish between CD30+ LPDs of LyP and pcALCL as well as other histologic mimics such as systemic ALCL and large cell transformation of MF. [Display omitted] DisclosuresAbdulla: Caris Life Licenses: Current Employment. Zain: Kiyoaw Kirin, Secura Bio, Seattle Genetics: Honoraria; Secura Bio, DaichiSankyo, Abbvie: Research Funding; Secura Bio, Ono , Legend, Kiyowa Kirin, Myeloid Therapeutics Verastem Daichi Sankyo: Consultancy.

Diagnostic Value of Plasmacytoid Dendritic Cells in Differentiating Pityriasis Lichenoides et Varioliformis Acuta From Lymphomatoid Papulosis.

Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) can often demonstrate clinical and histopathologic overlap. A recent study demonstrated significant plasmacytoid dendritic cell (pDC) recruitment in lesions of PLEVA, whereas another study reported minimal pDC recruitment in lesions of LyP. To confirm the possible diagnostic value of pDCs in differentiating PLEVA and LyP, we compared the presence and distribution of pDCs and myxovirus protein A (MxA) expression (an indirect assessment of pDC activity). In total, 19 cases of PLEVA (16 patients) and 14 cases of LyP (11 patients) were examined using immunohistochemical stains for anti-blood-derived dendritic cell antigen-2 and MxA. Individual semiquantitative scoring systems were used to assess the immunohistochemical results, and a Mann-Whitney test with a subsequent 2-tailed P test was performed for statistical analysis. No statistically significant difference in the number of pDCs in both groups was found. However, most PLEVA cases (84%) demonstrated intense and diffuse MxA expression, whereas LyP cases (71%) demonstrated weak patchy staining (P < 0.007). Our study suggests that although additional studies may be needed to determine whether pDCs are more relevant to the pathogenesis of PLEVA or LyP, pDC activity through MxA staining may play a role in differentiating PLEVA from LyP and may serve as a platform for additional studies.

Lymphomatoid papulosis: a clinicopathologic analysis and whole exome sequencing

Objective: To study the clinicopathologic characteristics and immunophenotype of lymphomatoid papulosis(LyP), followed by exon mutation analysis with focus on gene mutations involved in apoptosis pathway and other possible pathogenic genes. Methods: Clinical data analysis and immunohistochemical staining were carried out in 20 cases of LyP. Whole exome sequencing technology was employed in 2 cases of type C of LyP. Results: Of the 20 cases, there were 9 males and 11 females with a median age of 28.6 years. Nineteen patients presented with multiple papules and nodules, and one case presented with only one tumor nodule. Of the fifteen cases with available followed-up data, all were alive (20-155 months). Histologically, the tumors primarily involved the dermis and subcutaneous layer, in which 6 were type A, 3 were type B, 10 were type C and 1 was type D. Main infiltration patterns included wedge-shaped, band-like, sheets and large nodular. Immunohistochemistry showed that most cases expressed CD30 in the large tumor cells. Sixteen cases expressed CD3, 17 cases expressed CD4 and 8 cases expressed CD8. Sixteen cases expressed TIA1. Ten cases expressed GrB and 1 case expressed CD15. All but one case did not expressed CD20. All cases did not express ALK1.A total of 101 common non-synonymous mutations were detected in 2 cases of LyP type C by whole exome sequencing, including 87 missense mutations, 6 missense mutation/frame-shift deletions, 2 missense mutation/nonframe-shift deletions, 5 frame-shift deletions, 1 missense mutations/synonymous mutation. Syndecan-1(SDC1), COL4A1, Laminin-5 were involved in the extracellular matrix receptor pathway. Conclusions: Clinical presentations are crucial for the diagnosis of LyP. LyP has a favorable prognosis. SDC1, COL4A1 and Laminin-5 gene mutations may be associated with tumor recurrence or progression into a higher gradelymphoma.

Differential NFATc1 Expression in Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoma and Other Forms of Cutaneous T-Cell Lymphoma and Pseudolymphoma.

Primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSTCL) has recently emerged as a distinct clinicopathological entity. Because of a considerable degree of overlap with pseudolymphoma, the diagnosis is often challenging. Preliminary studies suggest that nuclear upregulation of calcineurin/nuclear factor of activated T cells (NFAT) may play a role in lymphomagenesis. 137 cases (70 males and 67 female, mean age = 55) of various forms of cutaneous T-cell and B-cell infiltration were evaluated for NFATc1 expression. The study comprised 18 cases of PCSTCL, 45 cases of mycosis fungoides (MF), 5 cases of lymphomatoid papulosis (LyP), 5 cases of anaplastic large-cell lymphoma (ALCL), 8 cases of other forms of peripheral T-cell lymphoma, not otherwise specified, 12 precursor lesions of MF (ie, cutaneous T-cell dyscrasias), 35 cases of pseudolymphomas, 8 primary cutaneous B-cell lymphoma, and 1 chronic lymphocytic leukemia. The number of cells exhibiting a nuclear stain was counted per 10 high-power field and 2-tailed statistical analysis was used for comparison of nuclear NFATc1 expression between primary PCSTCL and all other groups. A P-value <0.05 was considered to indicate statistical significance. All cases of PCSTCL showed nuclear staining for NFATc1 (mean = 296 ± 236) with no cases in which an exclusive cytoplasmic stain was observed. The cells exhibiting this staining pattern were oftentimes larger manifesting other features of a follicular helper T-cell phenotype, such as variable positivity for PD1, ICOS, CXCL13, and BCL6. In comparison, an exclusively cytoplasmic stain was observed in 29 cases of MF; in few cases, rare nuclear staining cells were observed averaging less than 10 per high-power field (P = 0.0001). These positive staining cases were not only limited to tumor-stage MF but also encompassed patch- and plaque-stage lesions and follicular variants of MF. The same pattern was observed in cases of T-cell dyscrasia (mean = 3 ± 3, P = 0.0001) and pseudolymphoma (mean = 2 ± 3, P = 0.0001), both revealing a dominant cytoplasmic staining pattern. In pseudolymphomatous folliculitis, a greater extent of nuclear staining for NFATc1 was observed compared with other forms of pseudolymphoma. No significant difference was seen between MF and T-cell dyscrasia or pesudolymphomas excluding pseudolymphotous folliculitis. Anaplastic large-cell lymphoma cases showed an almost exclusive cytoplasmic staining pattern with rare nuclear staining (mean = 55 ± 102, P = 0.0001); similar results were observed in LyP (mean = 17 ± 15, P = 0.004). Cutaneous B-cell lymphomas showed a similar extent of staining as that noted for PCSTCL. The greatest extent of staining was observed in chronic lymphocytic leukemia. A significant difference was noted between the extent of nuclear staining in PCSTCL and other forms of primary cutaneous T-cell lymphoma, type unspecified (mean = 22 ± 43, P = 0.0002), although not between PCSTCL and B-cell lymphoma. NFAT signaling plays a critical role in peripheral T-cell activation after T cell receptor engagement. When assessing T-cell-rich infiltrates where the differential diagnosis is largely between a PCSTCL and pseudolymphoma, a significant degree of nuclear staining of lymphocytes would be more in keeping with a diagnosis of PCSTCL. Upregulation of the NFAT pathway is not a feature of tumor progression in the setting of MF.

EXTRA-CORPOREAL PHOTOCHEMOTHERAPY IN THE TREATMENT OF LYMPHOMATOID PAPULOSIS AND FOLLICULOTROPIC MYCOSIS FUNGOIDES: CASE REPORTS

Aim: To assess clinical efficacy of extra-corporeal photochemotherapy (EPCT) in the treatment of rare lymphomas – lymphomatoid papulosis and folliculotropic mycosis fungoides. Materials and methods: This is a presentation of two cases of lymphomatoid papulosis and folliculotropic mycosis fungoides treated with EPCT with duration of follow-up 9 and 12 years. Extracorporeal photochemotherapy involved administration of 8-methoxypsoralen 0.6 mg/kg 1.5–2 hours before the initiation of intermittent flow separation of mononuclear cells using Haemonetics MCS+ blood cells separator and corresponding protocol. Cell suspension was exposed to UVA-radiation (λ=320–400 nm) using blood irradiator Julia (10–15 ml/min) during 30 minutes then re-infused. In total, 4 procedures were conducted every other day. Results: Both patients demonstrated positive effect involving regression of the rashes after 3 EPCT cycles. Subsequently, the patients received maintenance EPCT 2–3 times a year. Conclusion: High clinical efficacy of EPCT was demonstrated in 2 patients with lymphomatoid papulosis and folliculotropic mycosis fungoides after 9 and 12 years of follow-up.

γδ T-cell-rich variants of pityriasis lichenoides and lymphomatoid papulosis: benign cutaneous disorders to be distinguished from aggressive cutaneous γδ T-cell lymphomas.

T cells with a γδ phenotype have been associated with aggressive lymphomas. Yet, inflammatory skin disorders and low-grade lymphoproliferative disorders have rarely been described with a predominant γδ T-cell infiltrate. To review our experience and determine the clinical relevance of the γδ T-cell phenotype in lymphomatoid papulosis (LyP) and pityriasis lichenoides (PL). A retrospective dermatopathology file review looking for LyP and PL characterized by a γδ T-cell phenotype was performed. Clinical manifestations and course, histological features and molecular data were analyzed. Six of 16 cases of LyP and four of 23 cases diagnosed as PL during a 5-year period (2009-14) were identified. The median follow-up for the whole group was 16months (range 3-64), showing an indolent clinical course in all cases. The detection of a predominantly γδ T-cell phenotype in papular lymphoid-rich infiltrates in the absence of other lesions is not associated with a clinically aggressive course. γδ T-cell-rich variants of LyP and PL may reflect a spectrum of related conditions. This is a single academic centre retrospective chart review of a relatively small sample.

Recurrent Course and CD30 Expression of Atypical T Lymphocytes Distinguish Lymphomatoid Papulosis From Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-cell Lymphoma

© 2014 The Authors. doi: 10.2340/00015555-1806 Journal Compilation © 2014 Acta Dermato-Venereologica. ISSN 0001-5555 Lymphomatoid papulosis (LyP) is characterised by a chronic course of years to decades of recurrent papulonodular lesions, each of which undergoes spontaneous regression after weeks or months (1). Recently LyP type D was identified as a new histolopathological variant simulating a primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (pCAE-CD8+ CTCL) (2). Despite histologically alarming features, the patients have a clinical presentation and indolent course that are similar to those with typical cases of LyP.

Lymphomatoid papulosis in association with mycosis fungoides: A clinical and histopathologic review of five Taiwanese cases

Lymphomatoid papulosis (LyP) is a cutaneous CD30+ lymphoproliferative disorder characterized by recurrent, self-healing lesions with a chronic clinical course. Approximately 10–20% of the patients have lymphomas, including mycosis fungoides (MF). LyP in association with MF is not well documented in Taiwan. We aimed to describe the clinicopathologic characteristics of LyP with MF in a Taiwanese case series of LyP. A retrospective clinicopathologic study was performed on cases of LyP with MF diagnosed in our Department during the period 1990–2012. The diagnosis of LyP and MF were based on their characteristic clinical and pathologic features as well as correlation with the clinical course of the specific skin lesions. A total of 24 cases of LyP (10 males and 14 females, age 18–63 years, mean 40.4 years) were included. Multiple biopsies were often done in individual patients during the clinical course to establish the diagnosis of LyP and MF. LyP was further classified pathologically as type A ( n = 16), B ( n = 3), C ( n = 3), and mixed type with A&B ( n = 1) and A&C ( n = 1). Five cases (21%) also had MF; two had juvenile-onset LyP and three had juvenile-onset MF (one with hypopigmented MF, one with hyperpigmented MF, two with CD8+ LyP, and two with CD8+ MF). In the case of juvenile-onset hypopigmented CD8+ MF, the patient developed CD8+ LyP 25 years after the onset of MF and died of aggressive epidermotropic CD8+ lymphoma involving the skin and lung. MF occurred in five of the 24 cases (21%) in the present series of LyP. These five cases had several unusual clinical and pathologic features, including subtle or uncommon skin manifestation of MF and more frequent juvenile-onset and CD8 phenotype of LyP and/or MF lesions. Long-term follow-up and repeated biopsy of selected skin lesions are necessary for correct diagnosis and proper treatment of both diseases.

Investigation of molluscum contagiosum virus, orf and other parapoxviruses in lymphomatoid papulosis

Lymphomatoid papulosis (LyP) is a primary cutaneous CD30+ lymphoproliferative disorder with large, atypical CD-30+ cells, which despite their ominous appearance, also occur in reactive processes, such as CD30+ cutaneous lymphoid hyperplasia. As most causes of CD30+ cutaneous lymphoid hyperplasia are viral,1 we explored the possibility that poxvirus or parapoxvirus could be detected in lesions of LyP. Following University of Iowa Institutional Review Board approval, nine patients with a diagnosis of LyP that had available skin tissue blocks were included. For negative controls, two scar tissue samples were included. DNA was extracted from formalin-fixed, paraffin-embedded slides. Tissue was dewaxed by addition of xylene, vortexing, and centrifuging; xylene was removed and the pellet was rehydrated in 100% ethanol. After vortexing, centrifugation, and air drying, the sample was resuspended in digestion buffer and was incubated at 55°C for 4–6 hrs. Chelex-100 (BioRad) was added to a final concentration of 5%. The mixture was boiled 8 min, chilled 2 min, and centrifuged for 5 min at 4°C. The supernatant was transferred to a fresh centrifuge tube as template. Quantitative real-time polymerase chain reaction (q-PCR) was performed to detect Molluscum contagiosum virus p43K gene2; 10 ul of DNA was used in each assay. To ensure sufficient DNA was present and amplification was not due to presence of an inhibitor, the single copy RNaseP gene was detected by amplification of the DNA sample using a TaqMan RNaseP detection reagent kit (Applied Biosystems). A plasmid containing MCV p43K gene served as a positive control2. Parapoxvirus generic and orf virus specific q-PCR assays were also performed on the extracted DNA3, with positive controls using nucleic acid from Ovine Ecthyma Vaccine (Colorado Serum Company) and orf virus. No molluscum contagiosum, parapoxvirus generic, or orf virus DNA was detected the LyP samples or scars. Of the many infectious conditions associated with CD30+ cutaneous lymphoid hyperplasias, the most commonly associated viruses have been parapoxviruses (28.5%), herpes simplex and varicella zoster viruses (25%), and molluscum contagiosum virus (10.7%)1. Extrapolating these findings to true CD30+ lymphoproliferative disorders, previous studies have explored the possibility that LyP may represent a virally-induced cutaneous lymphoid hyperplasia. One analysis of LyP specimens by PCR demonstrated one out of nine LyP samples with detectable HHV 6 DNA, but no detectable HSV 1 and 2 or EBV DNA. 4. Recently, biopsy specimens of cutaneous lymphomas (including 3 cases of LyP) were assayed for Merkel cell polyoma virus, human polyomavirus type 6, human polyoma virus type 7, and trichodysplasia spinulosa-associated polyoma virus DNA by q- PCR; the cases of LyP were negative for all viral types5. As LyP and parapoxvirus and poxvirus virally-mediated CD30+ cutaneous lymphoid hyperplasias share overlapping clinical features (papular lesions, generally indolent course) and pathologic features (large, atypical CD30+ lymphoid infiltrates), LyP appears an intriguing candidate for induction by viral infection. However, the lack of detection of viral DNA in our LyP specimens argues against a link between parapoxviruses or molluscum contagiosum virus and LyP, although the role of sampling and stage of lesions should be considered.

Follicular lymphomatoid papulosis revisited: A study of 11 cases, with new histopathological findings

Follicular lymphomatoid papulosis (LyP) describes a variant of LyP with perifollicular infiltrates and some degree of folliculotropism of CD30(+) atypical lymphocytes. So far, only a few cases of follicular LyP have been described. Our goal was to study the clinicopathologic features of follicular LyP in a series of 11 cases (9 male, 2 female; age range 7-78 years, mean age 50 years). In all, 113 cases of LyP were reviewed to select cases showing follicular involvement. Histology was correlated with the clinical data to exclude cases of CD30(+) anaplastic large-cell lymphoma or folliculotropic mycosis fungoides. Six cases were classified as type C and 4 as type A, whereas the remaining case manifested epidermotropism of small lymphocytes in a background of a typical type A lesion (overlapping type A/B). Perifollicular infiltrates of CD30(+) atypical lymphoid cells were seen in all 11 cases, with infiltration of the follicular epithelium in 8 cases. Hyperplasia of the follicular epithelium was observed in 4 cases; ruptured hair follicles, in 3 cases; and follicular mucinosis, in 2 cases. In addition to hair follicle infiltration, atypical cells were recognized within sebaceous glands in 2 lesions. New findings were presence of numerous intrafollicular neutrophils in 2 patients, who clinically had pustules in addition to papules. Other histopathological features encountered included perieccrine infiltration (n = 5), focal subcutaneous involvement (n = 4), granulomatous inflammation (n = 3), epidermal hyperplasia (n = 2), and 1 each of infiltration of muscle bundles, numerous eosinophils in the infiltrate, and angiocentricity. This was a retrospective study. Follicular LyP is a variant of LyP with involvement of hair follicles, mostly in the form of perifollicular infiltrate with variable degree of folliculotropism. Other changes including hyperplasia of the follicular epithelium, rupture of hair follicle, and follicular mucinosis are less common. Rarely, intrafollicular pustules can be seen in the follicular epithelium; such lesions manifest clinically as pustules.

Exacerbation of lymphomatoid papulosis during rituximab therapy

We report two cases of lymphomatoid papulosis (LyP) occurring in conjunction with B-cell lymphoproliferative malignancies where the LyP was exacerbated during rituximab (anti-CD20 antibody)-based therapy. We postulate that the altered B-cell cytokine milieu acted to allow an exacerbation of the patient's concomitant T-cell disease and discuss the possible mechanisms by which this may have occurred.

Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T-cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co-expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.

Primary cutaneous CD30 positive T‐cell lymphoproliferative disorders with aberrant expression of PAX5: Report of three cases

Accurate diagnosis of lymphoma includes the assessment of lineage-specific markers. Hematopoietic and lymphoid tissues express PAX5 exclusively in pro-B-cell to mature B-cell stages. However, some mature PAX5+ T-cell lymphomas have been reported. We report three cases of primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPDs) with PAX5 expression: one cutaneous anaplastic large cell lymphoma (ALCL) and two cases of lymphomatoid papulosis (LyP). The three patients were 26 years old and female, 75 years old and female, and 65 years old and male. In all cases, Hodgkin's and Reed-Sternberg-like large lymphoid cells were present, positive for CD30, fascin, and PAX5, and negative for CD3, CD4, CD8, CD20, CD45RO, CD56, cytotoxic markers, and Epstein-Barr virus. The ALCL was accompanied by lymphadenopathy; the patient died of progressive disease 5 months after diagnosis. The LyP cases were localized in the skin with spontaneous regression. One case was diagnosed during pregnancy, transformed to ALCL, and ended in death 32 months after diagnosis despite multi-agent chemotherapy. This study is the first to address the clinical significance of PAX5+ primary cutaneous CD30+ T-cell LPDs. These cases were distinct regarding PAX5 expression and a relatively aggressive clinical course versus conventional primary cutaneous CD30+ T-cell LPDs.

Specificity of IRF4 translocations for primary cutaneous anaplastic large cell lymphoma: a multicenter study of 204 skin biopsies

Current pathologic criteria cannot reliably distinguish cutaneous anaplastic large cell lymphoma from other CD30-positive T-cell lymphoproliferative disorders (lymphomatoid papulosis, systemic anaplastic large cell lymphoma with skin involvement, and transformed mycosis fungoides). We previously reported IRF4 (interferon regulatory factor-4) translocations in cutaneous anaplastic large cell lymphomas. Here, we investigated the clinical utility of detecting IRF4 translocations in skin biopsies. We performed fluorescence in situ hybridization (FISH) for IRF4 in 204 biopsies involved by T-cell lymphoproliferative disorders from 182 patients at three institutions. In all, 9 of 45 (20%) cutaneous anaplastic large cell lymphomas and 1 of 32 (3%) cases of lymphomatoid papulosis with informative results demonstrated an IRF4 translocation. Remaining informative cases were negative for a translocation (7 systemic anaplastic large cell lymphomas; 44 cases of mycosis fungoides/Sézary syndrome (13 transformed); 24 peripheral T-cell lymphomas, not otherwise specified; 12 CD4-positive small/medium-sized pleomorphic T-cell lymphomas; 5 extranodal NK/T-cell lymphomas, nasal type; 4 gamma-delta T-cell lymphomas; and 5 other uncommon T-cell lymphoproliferative disorders). Among all cutaneous T-cell lymphoproliferative disorders, FISH for IRF4 had a specificity and positive predictive value for cutaneous anaplastic large cell lymphoma of 99 and 90%, respectively (P=0.00002, Fisher's exact test). Among anaplastic large cell lymphomas, lymphomatoid papulosis, and transformed mycosis fungoides, specificity and positive predictive value were 98 and 90%, respectively (P=0.005). FISH abnormalities other than translocations and IRF4 protein expression were seen in 13 and 65% of cases, respectively, but were nonspecific with regard to T-cell lymphoproliferative disorder subtype. Our findings support the clinical utility of FISH for IRF4 in the differential diagnosis of T-cell lymphoproliferative disorders in skin biopsies, with detection of a translocation favoring cutaneous anaplastic large cell lymphoma. Like all FISH studies, IRF4 testing must be interpreted in the context of morphology, phenotype, and clinical features.

Investigation on clinicopathologic features of lymphomatoid papulosis

To investigate the clinicopathologic features, immunophenotype and prognosis of lymphomatoid papulosis (LyP). Clinicopathologic analysis, immunohistochemical staining (LSAB and EliVision method) and in situ hybridization for EBER were undertaken in this study. Thirteen cases of LyP were studied, derived from six male and seven female patients with a median age of 26.4 years. The most common presentation was multiple symptomless papules or nodules, involving predominately the extremities and trunks. Histologically, the tumor primarily involved the dermis and subcutaneous layer. Six tumors were type A, one was type B and six were type C. The main infiltration patterns were wedge-shaped, band-like, sheet-like or nodular. There was epidermotropism in eight cases. Immunohistochemical staining showed that the large tumor cells in all 12 types A and C cases expressed CD30. All 13 cases expressed two to three T-cell associated antigens (CD3, CD5 or CD45RO) and one to three cytotoxic granule associated antigens (TIA-1, GrB or Perforin). All cases expressed CD4, four expressed CD8, and one expressed CD15. Only one case expressed CD20; and all cases were negative for ALK-1. The tumor cells showing epidermotropism had CD3(+), CD4(+) and CD8(-) phenotype in most cases. Only one case was EBER1/2 positive. Follow up information was available in 12 patients; all were alive at the end of the follow up period. LyP has distinctive clinicopathologic features and immunophenotype with favorable prognosis. In types A and C, the atypical cells showing epidermotropism were similar to those in MF, these cells possess cerebriform and hyperchromatic nuclei. The epidermotropic tumor cells and the CD30(+) large cells may be derived from different clones. EB virus may not be correlated with LyP.

Resolution of CD8+ Lymphomatoid Papulosis After Surgical Excision of the Type AB-Thymoma

Lymphomatoid papulosis (LyP) is a disease characterized by cyclic eruptions of papulonodular lesions, which undergo spontaneous healing. Lymphoid malignancies are present in 10%-15% of cases. The type AB thymoma is an epithelial neoplasm composed of both type A (lymphocyte-poor) and type B (lymphocyte-rich) areas. Chemokines are chemotactic cytokines, responsible for leukocyte motility and direct movement. Interactions between chemokines and their receptors have been correlated with homing of lymphoma cells to various tissues. We describe a patient whose type B LyP CD8 lesions completely resolved after surgical removal of type AB thymoma. The chemokine profile was similar in both tissues: thymus- and activation-regulated chemokine and CCR4 were focally positive in the thymoma. Thymus- and activation-regulated chemokine was positive in the epidermotropic cells and in the majority of the dermal lymphocytes in the LyP specimen, whereas CCR4 was focally positive in the dermal lymphocytes. Monokine induced by interferon-g (Mig) staining showed strong positivity in the dermal lymphocytes and in localized areas of the thymoma, but an immunostain for the Mig receptor (CXCR3) highlighted only a few scattered cells in both tissues (less than 3%). Both tissues were negative for regulated upon activation, normal T-cell expressed and secreted (RANTES) and CCR3. In summary, we report the association of a CD30-negative CD8-predominant LyP and a type AB thymoma, with similar chemokine profiles. The rarity of both conditions and the precise regression of LyP after removal of the thymoma argue against a coincidental observation. We recommend that a search for thymoma be included in the workup of LyP. Further chemokine profiling in other cases of LyP may assist in understanding their role in this disease.

Clusterin Expression Correlates With Stage and Presence of Large Cells in Mycosis Fungoides

Clusterin expression is common in systemic and cutaneous anaplastic large cell lymphoma (ALCL). Mycosis fungoides (MF) in large cell transformation can resemble ALCL. In this study, we immunohistochemically assessed for clusterin in 97 skin biopsy specimens, including 70 MF cases and 27 other cutaneous neoplasms including ALCL, peripheral T-cell lymphoma unspecified (PTCL), and lymphomatoid papulosis (LyP). Clusterin was positive in 36 (51%) of 70 cases of MF and correlated with clinical stage in 68 cases: 3 of 21 stage I, 11 of 20 stage II, and 23 of 27 stage III/IV. Clusterin expression also correlated with type of skin lesion (3/19 patch, 13/28 plaque, and 20/23 tumor/erythroderma) and number of large cells (6/30 small cell, 12/18 with increased large cells, and 18/22 with large cell transformation). Clusterin expression was not specific for MF as it also was positive in 3 of 3 cases of LyP, 2 of 2 systemic ALCL cases involving skin, 7 of 16 cutaneous ALCLs, and 1 of 6 PTCLs.