Diagnosis Of Lymphomatoid Papulosis Research Articles

An Unusual Type of Lymphomatoid Papulosis Presenting in Pregnancy: Risk-Benefit Analysis of Antepartum Treatment [18H

INTRODUCTION: Lymphomatoid papulosis (LyP) has an incidence of 2 per 1,000,000 and is associated with lymphoproliferative disorders. Type E, characterized by angioinvasion, is the rarest subtype and is associated with CD30 and CD8 expression. LyP is associated with immune compromising disorders, making pregnancy a potential setting for presentation. We present one of the first cases of LyP type E in pregnancy. METHODS: Case: 30-year-old G5P3, with a pregnancy complicated by a history of hemolysis, elevated liver enzymes and low platelet count syndrome in a previous pregnancy, presented in early pregnancy with a two month history of diffuse painful skin lesions. As the pregnancy progressed, the lesions spread and would blister and ulcerate before resolving. Biopsy returned with CD30+ angioinvasive LyP type E. Prednisone and topical steroids provided minimal symptomatic improvement. Peginterferon alfa-2a was offered as an alternative therapy; however, was deferred until after delivery. CONCLUSION: Appropriate diagnosis of LyP and subtype as well as multi-disciplinary follow-up is essential given possible associated lymphoproliferative disorders. Treatment may involve more risk than benefit and has not been proven to prevent associated malignancy necessitating individualized risk-benefit analysis. Conservative treatment is preferred, even in significantly symptomatic pregnant patients. In some severely symptomatic patients, peginterferon alfa-2a may be considered with a better safety profile compared to other agents in pregnancy. The angiodestructive nature of type E may be associated with pregnancy complications including those on the preeclampsia spectrum. These pregnancies may require closer monitoring and the consideration of aspirin prophylaxis. Early diagnostic biopsy will allow for timely intervention.

Lymphomatoid papulosis.

Lymphomatoid papulosis (LyP) is a non-aggressive skin disorder characterized by papulonodular injuries, sometimes necrotic, often scattered, relapsing, which frequently regress spontaneously. LyP represents about 12% of cutaneous lymphomas. The etiology of LyP is unknown. Based on its histopathology, in 2018, the World Health Organization (WHO) classified LyP into six types with similar prognosis (A,B,C,D,E and DUSP22). Once the diagnosis of LyP has been made, having an excellent prognosis, this pathology must be managed mainly with a "watch and wait" strategy. Treatment should be given only in the presence of diffuse, symptomatic lesions with disfiguring evolution, with the aim of reducing time of resolution and preventing recurrences or the formation of new lesions.

Lymphomatoid papulosis localized to the oral mucosa: case report and literature review

Introduction: Lymphomatoid papulosis is a primary CD 30+ cutaneous lymphoproliferation. Observation: We report the case of a 39-year-old patient who presented with ulcers on the back of the tongue, gums, buccal mucosa, and soft palate, which evolved as spontaneously regressive flare-ups. The diagnosis of inflammatory bowel disease was initially proposed. Several years later, the patient presented an ulcer on the left middle finger. Histological examination confirmed the diagnosis of lymphomatoid papulosis. Discussion: This chronic dermatosis manifests a single rash or multiple papulonodular rashes, evolving as spontaneously regressive flare-ups. Mucosal involvement is rare, and no prognostic factor for this location has been highlighted to this date. Pathological examination is essential. Conclusion: The mucosal involvement of lymphomatoid papulosis is one of the diagnoses to be considered for recurrent mouth ulcers.

Associated Hematolymphoid Malignancies in Patients With Lymphomatoid Papulosis: A Canadian Retrospective Study.

Lymphomatoid papulosis is one of the primary cutaneous CD30+ T-cell lymphoproliferative disorders. Although considered a benign disease, lymphomatoid papulosis has been associated potentially with an increased risk of secondary hematolymphoid malignancies. The aim of this study was to assess the clinical characteristics and histologic subtypes of lymphomatoid papulosis, identify the prevalence and types of secondary hematolymphoid malignancies, and determine the potential risk factors for development of these hematolymphoid malignancies. A retrospective chart review was performed for all histologically confirmed cases of lymphomatoid papulosis between 1991 and 2016. Seventy patients with lymphomatoid papulosis were identified. Thirty patients (43%) experienced a secondary hematolymphoid malignancy. Twenty-four (80%) of the hematolymphoid malignancies occurred after the onset of lymphomatoid papulosis. Older age at diagnosis of lymphomatoid papulosis, male sex, histology type B, and the presence of T-cell receptor gene rearrangement are associated with higher risk of developing hematolymphoid malignancy. Lymphomatoid papulosis is associated with increased risk of developing secondary hematolymphoid malignancies, particularly mycosis fungoides and cutaneous anaplastic large cell lymphoma.

Lymphomatoid papulosis as a harbinger of chronic lymphocytic leukemia

Dear Editor, We report on a patient with a new diagnosis of lymphomatoid papulosis (LyP) who was subsequently diagnosed with chronic lymphocytic leukemia (CLL). LyP is a CD30+ lymphoproliferative disorder characterized by recurrent papulonodular eruptions that appear malignant histologically but usually follow a benign and indolent course [1]. In 9–18% of patients, LyPmay progress to malignancies such as mycosis fungoides, anaplastic large cell lymphoma, and Hodgkin’s disease (Table 1) [2–7]. To date, there has been one report of LyP associated with acute myeloblastic leukemia (AML) [8] and one report associated with small-cell lymphocytic B cell lymphoma [9]. A previously healthy 78-year-old Caucasian woman presented to the dermatology clinic at our institution with a 5month history of intermittent eruptions of a pruritic rash in the inguinal area, back, thighs, and legs. The rash consisted of erythematous, polymorphic papules that increased in size and coalesced into plaques over the lifespan of the lesion (Fig. 1). The skin lesions appeared in crops and spontaneously regressed within 2 months. In the referring physician’s assessment, two separate skin biopsies were performed and found to be inconclusive, demonstrating spongiotic dermatitis with an inflammatory infiltrate in the dermis. The patient received multiple steroid injections for a presumptive diagnosis of vasculitis, resulting in only temporary relief of symptoms. Laboratory work-up at that time was notable for a lymphocytosis to 62 % (reference range, 12–46 %) and an elevated absolute lymphocyte count of 4.3 K/ μL (reference range, 0.7–4.0 K/μL). However, the patient was evaluated by a hematologist, and malignancy was ruled out due to an absolute lymphocyte count less than 15,000 and no evidence of adenopathy, thrombocytopenia, anemia, or organomegaly. Due to recurrence of lesions, the patient was referred to our institution for further evaluation. She reported feeling well and denied fatigue, fever, chills, or weight loss. A third biopsy showed nonspecific findings and negative direct immunofluorescence. Despite initiating therapy with oral prednisone, the lesions continued to recur, and a fourth skin biopsy was obtained. This demonstrated a superficialto mid-dermal mixed inflammatory infiltrate consisting of predominantly lymphocytes and histiocytes, with few neutrophils. The lymphocytes were large and atypical (Fig. 2a). Immunohistochemical stains were performed and stained positively for CD3, CD20, and CD30. The presence of CD3 highlights a predominance of T cells, whereas CD20 highlights a background of B cells. Staining for CD30 highlighted the larger, atypical Reed-Sternberg-like cells intermingled with inflammatory cells, with the background inflammatory cells greatly outnumbering the CD30-positive tumor cells (Fig. 2b). These findings were consistent with type A lymphomatoid papulosis. Methotrexate 5 mg weekly was added to her regimen, and she was referred to the lymphoma clinic for work-up for underlying malignancy. Upon reevaluation, laboratory tests revealed an elevated white blood cell count to 20.8 K/μL, with an absolute lymphocyte count of 12.2 K/μL (reference range, 1.0– 5.1 K/μL). Flow cytometry of peripheral blood revealed expression of T cell antigen 5 and B cell antigens CD19, CD20, and CD23. There was strong intensity staining for CD45, and no significant CD34-positive blast population was identified. These findings were consistent with a monoclonal CD5-positive B cell lymphocytosis and were consistent with CLL, Rai stage 0. Thinking that the skin lesions could be a manifestation of her underlying CLL, the patient was begun on a single agent bendamustine 90 mg/m. C. S. Ahn : C. S. Orscheln :W. W. Huang (*) Department of Dermatology, Wake Forest School of Medicine, 4618 Country Club Road, Winston-Salem, NC 27104, USA e-mail: whuang@wakehealth.edu DOI 10.1007/s00277-014-2064-6 Ann Hematol (2014) 93:1923–1925

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.

Intravenous immunoglobulin therapy in vasculitic ulcers: a case of polyarteritis nodosa.

IntroductionPolyarteritis nodosa (PAN) is a systemic necrotizing medium-size-vessel vasculitis with variable clinical manifestations. Diagnosis is confirmed by histology or angiography. The mainstay of treatment is corticosteroids alone or combined with cyclophosphamide (CYF).Case reportSeventy-one-year-old female, follow-up started in 1997 at the age of 56 for suspected relapsing febrile viral exanthema. Skin biopsy was performed and the diagnosis of lymphomatoid papulosis was made, with complete response to treatment with dapsone. In 2005, she presented with arthralgia, lower limb (LL) edema, livedo reticularis and elevated erythrocyte sedimentation rate (ESR). PAN was confirmed on histology and visceral angiography; antineutrophil cytoplasmic antibodies (ANCA) were negative. She responded to prednisolone but relapsed in 2006. Twelve cycles of CYF were administered, with clinical, angiographic and analytical improvement. In 2008, a new relapse occured with LL neuropathic pain and ESR elevation. Electromyogram (EMG) confirmed axonal sensory polyneuropathy (PNP). Azathioprine was started with a poor response. A second EMG, 12 months later in 2009 still evidenced PNP, and nerve biopsy confirmed vasculitic neuropathy. In 2010, she had ulcers in LL and iron-deficient anemia. She started intravenous immunoglobulin (IVIG) for six cycles, achieving ulcer healing, absence of pain, no anemia and ESR normalization.DiscussionIVIG therapy has proven benefit in Kawasaki disease, also showing efficacy in refractory ANCA-associated vasculitis. In PAN, only very few case reports show benefit. In this case, IVIG therapy induced total remission of LL ulcers and PNP, suggesting that it may be useful in selected cases of refractory PAN.

Lymphomatoid papulosis: is a second lymphoma commoner among East Asians?

Lymphomatoid papulosis (LyP) is a low-grade cutaneous lymphoma, which lies within the spectrum of primary cutaneous CD30-positive lymphoproliferative disorders. Around 10-20% of LyP cases are associated with a second lymphoma. To analyse a cohort of Asian patients with LyP, diagnosed from 1987 to 2007 at the National Skin Centre (NSC), Singapore, in terms of epidemiology, treatment and association with a second lymphoma. Patients were identified through the NSC clinical and histological databases. During this period, 13 patients were diagnosed with LyP based on clinicopathological criteria. The mean age at diagnosis was 41 years, the male : female ratio was 2.3 : 1, and 92% of the patients were Chinese. Recurrent papulonecrotic lesions were present for a mean of 3 years before diagnosis. Treatment of LyP comprised monotherapy (n = 4) or combination therapy (n = 9) using corticosteroids, oral antibiotics, methotrexate and/or phototherapy. Mean duration of follow-up was 6.4 years. Eight patients (61.5%) were diagnosed with a second lymphoma, either before (n = 2), concurrently with (n = 1) or after (n = 5) the diagnosis of LyP. Mycosis fungoides (MF) was the commonest lymphoma (78%, n = 7), followed by primary cutaneous anaplastic large-cell lymphoma (12%, n = 2). There was one death (mortality rate 7.7%), which occurred in a patient who had developed stage IIA MF after LyP, which subsequently progressed to systemic T-cell lymphoma. LyP is a chronic, relapsing disease with considerable morbidity, but an overall good prognosis. A strikingly large proportion of our Asian patients (61.5%) had a second lymphoma, compared with previous studies. This emphasizes the importance of regular lifetime surveillance for associated lymphomas in all patients with LyP.

Lymphomatoid papulosis with CD1a+ dendritic cell hyperplasia, mimicking Langerhans cell histiocytosis

Although CD1a+ dendritic cells (DC) in cutaneous T-cell lymphomas (CTCL) have been well documented, the presence of large numbers of DC within lymphoid infiltrates can pose a diagnostic difficulty. We present a case of a 70-year-old man with a 3-year history of recurrent red papules and plaques on the extremities and trunk that was referred to our institution, with the diagnosis of Langerhans cell histiocytosis. Skin biopsies showed a wedge-shaped cellular infiltrate in the superficial and deep dermis consisting of two cell populations. Most prominent were clusters of epithelioid cells with grooved nuclei and abundant eosinophilic cytoplasm, which stained with antibodies to CD1a and S-100. A second, less prominent population of atypical lymphocytes, some with enlarged, hyperchromatic and convoluted nuclei, were intermixed. The latter were positive for CD30, CD3 and CD5 and negative for CD20, CD34, CD68, ALK-1 and TdT. T-cell receptor gene rearrangement studies confirmed a clonal T-cell population, which with the clinical history was consistent with the diagnosis of lymphomatoid papulosis. While previous studies have shown an increased density of dermal DC in CTCL, we believe that this represents the first report of an unusually florid DC proliferation mimicking Langerhans cell histiocytosis and masking a lymphoproliferative disorder.

Fine needle aspiration cytology of high grade T-cell lymphomas in human T-lymphotropic virus type 1 carriers.

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.

Accuracy in Diagnosis of Lymphomatoid Papulosis

This study was undertaken to assess the accuracy of histologic diagnosis of lymphomatoid papulosis (LyP), which may be confused with malignant lymphoma or other entities. It is essential that accurate diagnoses be made because LyP may be a marker for malignant lymphoma. All 15 examples of LyP reviewed in a dermatopathology laboratory during a 14-year period and 180 histologic sections of tissue that could be confused with LyP were reviewed. Criteria for diagnosis of LyP were applied without benefit of clinical history, and revised diagnoses were made where indicated. Clinical follow-up information was obtained and original accuracy of diagnosis was assessed by comparing clinical courses with original histologic diagnoses. In cases of LyP in which numerous atypical lymphoid cells were present, 100% accuracy was noted. When fewer atypical lymphoid cells were present and inflammatory cell infiltrates were less dense, the diagnosis was less certain. Overall, a 64% correlation of clinical course and histologic diagnosis of LyP was noted. We conclude that the histologic diagnosis of LyP is generally reliable and accurate; however, in some cases a precise diagnosis cannot be made with certainty. Cases with fewer atypical lymphoid cells may fail to correlate well with the classic course of LyP and may represent a variant or histologic simulator.