Fistulizing Epstein–Barr virus‐positive plasmablastic lymphoma in an HIV‐positive man

Plasmablastic lymphoma (PBL) is an unusual subtype of non‐Hodgkin lymphoma recently classified as a diffuse immunoblastic lymphoma with a plasma‐cell immunophenotype. Originally described in the oral cavity of HIV‐positive patients, it has also been recognized to occur rarely at other sites. We describe a previously unreported fistulizing presentation of Epstein–Barr virus (EBV)‐positive PBL, reviewing its association with HIV‐1 infection and its importance as an AIDS‐defining malignancy.     

Recurrent and self-healing cutaneous monoclonal plasmablastic infiltrates in a patient with AIDS and Kaposi sarcoma

Infection with human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin lymphoma. Plasmablastic lymphoma (PBL) is a rare variant of diffuse large cell lymphoma that often involves the oral cavity of HIV+ patients. It is characterized by immunoblastic morphology and plasma cell phenotype. Cutaneous involvement in PBL appears to be rare. We report a 44-year-old man with AIDS and Kaposi sarcoma (KS) previously treated with doxorubicin who, following treatment with highly active antiretroviral therapy, developed an erythematous infiltrated nodule on the right arm. Histology showed subcutaneous fat necrosis and clusters of atypical large plasma cells (plasmablastic cells). Immunohistochemistry revealed lambda light chain restriction. Epstein-Barr virus (EBV) mRNA was detected by in situ hybridization within the plasmablastic cells. Polymerase chain reaction amplification with specific primers for human herpesvirus 8 (HHV-8) performed on the skin biopsy specimen detected a specific band. A complete screening (bone marrow biopsy, computed tomographic scan, radiological survey) disclosed no abnormalities. The lesion resolved spontaneously after 3 months. Two years later an infiltrated plaque developed on the abdominal wall. The clinical and histopathological features of this new lesion were similar to those observed 2 years previously. No evidence of extracutaneous involvement was detected. The lesion again resolved spontaneously after 25 days. PBL may be seen in patients with transplants or receiving chemotherapy, but is usually observed in patients with advanced AIDS. The observation of recurrent self-healing EBV- and HHV-8-associated cutaneous monoclonal plasmablastic infiltrates, in a patient with AIDS and KS, expands the clinical spectrum of AIDS-associated plasmablastic lymphoproliferative disorders.     

Cutaneous plasmablastic lymphoma in an HIV-positive male: an unrecognized cutaneous manifestation

Plasmablastic lymphoma (PBL) is a rare and relatively new entity originally described in HIV-infected individuals. This subset of Epstein-Barr-virus (EBV)-related non-Hodgkin lymphomas is now regarded as a distinct clinicopathological category of AIDS-associated lymphomas occurring preferentially in the oral cavity and showing a poor prognosis. We describe for the first time an EBV-associated PBL with an isolated cutaneous distribution on the lower extremities in an HIV-infected heterosexual male and point to the unique clinical, morphological and immunophenotypic characteristics of this lymphoma. The patient presented with fast growing solid and livid nodules on both legs. The large, blastic tumor cells showed the following immunophenotype: CD138+, CD45+, CD20-, CD10-, CD3-, CD30-, bcl-2-, bcl-6-, LMP-1- and EMA-. The proliferation fraction (Mib-1) was >90%. EBV association was demonstrated by in situ hybridization (EBV-encoded RNAs 1/2). Polymerase-chain-reaction-based DNA analysis demonstrated a clonal IgH rearrangement in the absence of a bcl-2/IgH translocation. PBL in HIV patients may occur not only in the oral cavity, but can probably involve any other organs including the skin.     

ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin

Systemic cases of the CD30‐positive T‐cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)‐positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK‐negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79‐year‐old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B‐cell lymphoma. In addition, bcl‐2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK‐negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T‐cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis. Rieger K, Polidore T, Warnke R, Kim J. ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin.     

Primary Cutaneous CD30 Positive Anaplastic Large Cell Lymphoma in an Adolescent

Abstract: We present a case of a 14‐year‐old boy with a large ulcerated plaque on the scalp for 6 months, who was found to have primary cutaneous CD30‐positive, anaplastic kinase‐negative, anaplastic large cell lymphoma with post‐auricular lymphadenopathy. MRI, bone marrow biopsy, and laboratory data demonstrated no other systemic involvement. He was treated with radiation and low‐dose oral methotrexate, with improvement of the lesion and lymphadenopathy. Very few cases of primary cutaneous CD30‐positive anaplastic large cell lymphoma in the pediatric population have been reported, and our case represents one of the first pediatric patients with local lymph node involvement.     

Extracavitary primary effusion lymphoma presenting as a cutaneous tumor: a case report and literature review

Primary effusion lymphoma is an unusual form of aggressive B‐cell lymphoma universally associated with human herpesvirus 8 (HHV8) that involves mostly human immunodeficiency virus (HIV)‐infected patients. Characteristically, it presents as a malignant serous effusion involving body cavities, but without associated tumor mass. Exceptionally, HHV8‐positive lymphomas with features identical to primary effusion lymphoma may present as mass lesions in the absence of cavity effusions along the course of the disease, and are regarded as extracavitary or solid variants of the disorder. These rare forms are extremely rare in the skin. We report a case of extracavitary primary effusion lymphoma arising in a HIV‐infected male, who presented with two subcutaneous masses involving the skin of the abdominal and inguinal regions as the first manifestation of the process. Kaposi sarcoma was not present in the skin surface or mucous membranes. Extensive studies failed to demonstrate involvement of other organs and the case was considered as an example of extracavitary primary effusion lymphoma originating primarily in the skin. Herein, we review the few reported cases of solid primary effusion lymphoma involving the skin in order to delineate the clinicopathologic, immunohistochemical and molecular characteristics of this rare lymphoma in the skin.     

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.     

Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy

Background Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow‐up are lacking. Objectives To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin. Methods Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow‐up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed. Results Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow‐up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B‐cell lymphoma (one case) and peripheral T‐cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH. Conclusions The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long‐term follow‐up are therefore warranted in such patients.     

The challenging diagnosis of overlapping oral primary/secondary syphilis with nonreactive serology

The prevalence of oral syphilis, known as “the great imitator” because of its diagnostic complexity and varied clinical manifestations, is increasing worldwide, particularly in people living with HIV (PLWH), who could present false-negative serological results. Although some studies have described the variable presentation of oral syphilis in the context of HIV infection, the difficulty in distinguishing between the primary and secondary stages, clinically and histopathologically, underscores the need to describe atypical cases. We report the case of a 28-year-old HIV-positive man presenting with a 3-month history of painless white/red ulcerated lesion on the soft palate. Physical examination revealed an ulcerated lesion with local signs of inflammation. Initial biopsy revealed a nonspecific inflammatory process and immunohistochemistry (IHC) using anti-Treponema pallidum antibodies showed negative results. The results of serological tests for syphilis (Venereal Disease Research Laboratory and fluorescent treponemal antibody-absorption test) were negative on repeated occasions. Nonetheless, polymerase chain reaction (PCR) assay and subsequent IHC for T. pallidum showed positive results, confirming the diagnosis of oral syphilis. This case illustrates that the diagnosis of oral syphilis is challenging in the absence of serological evidence, and specific tests such as PCR and IHC are useful complementary diagnostic tools.     

Cutaneous lesions as the first manifestation of systemic follicular lymphoma in an HIV patient

Human immunodeficiency virus (HIV) patients have an increased incidence of lymphomas, particularly when there is a significant immunosuppression. Most commonly, they are non-Hodgkin B cell type with a high or intermediate grade and have an extranodal presentation. We report the case of a 38-year-old man with HIV infection who presented with a 1-year history of a painless tumor on the back and lymphadenopathies. The diagnosis of B cell lymphoma follicle center cell type was established by skin biopsy. Staging included a bone marrow biopsy revealing infiltration by the lymphoma and a whole-body computed tomographic scan showing multiple cervical and axillary lymphadenopathies with necrotic center. Biopsy of an axillary lymph node revealed caseating epithelioid granulomas and Ziehl-Neelson staining was positive for acid-fast bacilli. The patient started therapy for tuberculosis and polychemotherapy for lymphoma with complete response. This report illustrates a case of simultaneous occurrence of tuberculosis and systemic follicular lymphoma presenting in skin in an HIV patient.     

Úlceras orales como manifestación clínica de proceso linfoproliferativo asociado a metotrexato en una paciente con artritis reumatoide

Methotrexate-associated lymphoproliferative disorders are a heterogeneous group of lymphoid proliferations or lymphomas that develop in patients with autoimmune diseases treated using methotrexate.These lymphoproliferative disorders are often associated with Epstein-Barr virus infection and occasionally regress after the withdrawal of methotrexate therapy. The lymphoproliferative disorder in this case was diffuse large B-cell lymphoma, unusually presenting as oral ulcers in a 79-year-old woman on treatment with methotrexate for longstanding rheumatoid arthritis. Latent membrane protein 1 positivity was detected by immunohistochemistry and Epstein-Barr-virus encoded small RNA positivity by chromogenic in situ hybridization. Clonality was confirmed by immunohistochemistry (κ light-chain restriction), polymerase chain reaction (monoclonal immunoglobulin H gene rearrangement), and capillary electrophoresis (GeneScan). Staging procedures were negative. Withdrawal of methotrexate therapy led to complete remission within 6 weeks, and the patient is alive and disease-free 18 months after the diagnosis was made.The oral cavity is not often involved in the initial presentation of methotrexate-associated lymphoproliferative disorders, and presentation with intraoral ulcers is very rare. We have performed a review of the literature on methotrexate-associated lymphoproliferative disorders presenting as ulcers in the oral cavity.     

Two distinct variants of mycosis fungoides (MF): Folliculotropic MF and erythrodermic MF

Mycosis fungoides (MF) is the most frequent type of cutaneous T‐cell lymphoma. Folliculotropic MF (fMF) and erythrodermic MF (eMF) are two distinct variants of MF. Both variants have been considered aggressive and most cases are less responsive to standard skin‐directed therapies than classical MF. We, however, experienced many cases with fMF or eMF who showed indolent clinical courses. In this article, we reviewed 10 cases with fMF and 13 cases with eMF who came to our department between 2005 and 2017. In patients with fMF, monotherapy with topical corticosteroid was effective in two cases (20%) and ultraviolet phototherapy with oral retinoid controlled disease activity in two cases (20%). Five patients with eMF (38%) responded well to ultraviolet phototherapy. In conclusion, patients with early fMF and a subgroup of eMF patients have an indolent disease course, as was proposed among the specialists. Skin‐directed therapies are preferable rather than aggressive treatment in those cases.     

Myxoid variant of primary cutaneous anaplastic large cell lymphoma: First 2 cases

Anaplastic large cell lymphoma (ALCL) is a CD30+ T‐cell non‐Hodgkin lymphoma with 2 main clinical presentations: primary cutaneous ALCL (pcALCL) and systemic ALCL (sALCL). While rare cases of myxoid sALCL have been reported, there are no previous cases of myxoid pcALCL reported. We present 2 unusual cases of pcALCL showing prominent collections of dermal mucin closely intermingling with the anaplastic lymphocytes. Patient 1 was a 30‐year‐old woman who presented with ulcerated nodules on her neck, abdomen, chest and shoulders. A systemic lymphoma was excluded by physical examination, positron emission tomography and computed tomography (PET‐CT) scan, as well as by bone marrow biopsy and flow cytometry studies. The patient was closely followed‐up for 10 months without evidence of systemic involvement. The biopsy showed diffuse infiltration of the dermis by a CD2+, CD30+, anaplastic lymphoma kinase (ALK)‐negative ALCL. Patient 2 was a 55‐year‐old woman who presented with a single nodule on her right arm. A systemic lymphoma was excluded by physical examination as well as by a PET‐CT scan. The biopsy showed diffuse and dense lymphoid infiltration of the whole biopsy by a CD3+, CD4+, CD30+, ALK‐negative ALCL. The atypical lymphocytes were intermingled with large amounts of dermal stromal mucin.     

Cutaneous presentation of post‐renal transplant lymphoproliferative disorder: a series of four cases

We report detailed histological and molecular characteristics of four post transplant lymphoproliferative disorders (PTLD) presenting in the skin of renal transplant patients, and their clinical outcome. Three had B‐cell lymphomas (cases 1–3), and one had a T‐cell lymphoma (case 4). All B‐cell lymphomas showed Epstein‐Barr virus (EBV) by immunohistochemistry (IHC) or in situ hybridization (ISH). Cases 1 and 2 were large cell lymphomas, and case 3 a plasmacytoma. Case 1 showed light chain restriction and heavy chain gene rearrangement by polymerase chain reaction (PCR). The patient was then diagnosed with an abdominal lymphoma and died of sepsis. Case 2 had no recoverable DNA. Case 3 had a plasmacytoma that showed monoclonal light chain restriction on IHC and an oligoclonal heavy chain rearrangement by PCR. In cases 2 and 3, the lesions regressed following reduction of immunosuppression, and died 1.5 and 8 years later from unrelated medical causes. Case 4 was a CD 30+ anaplastic large T‐cell lymphoma with no EBV detected by IHC, ISH and PCR, and died of heart failure 2 years later. Cutaneous manifestations of PTLD are rare, show wide array of clinical and pathological features, and generally have a favorable prognosis. EBV appears to be associated only with B‐cell cutaneous lymphomas Salama S, Todd S, Cina DP and Margetts P. Cutaneous presentation of post‐renal transplant lymphoproliferative disorder: a series of four cases.     

Eosinophilic pustular folliculitis: A published work‐based comprehensive analysis of therapeutic responsiveness

Eosinophilic pustular folliculitis (EPF) is a non‐infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression‐associated EPF, which is subdivided into HIV‐associated (IS/HIV) and non‐HIV‐associated (IS/non‐HIV); and (iii) infancy‐associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non‐HIV and infancy‐associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non‐HIV and infancy‐associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei‐to (a Chinese–Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin‐resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF.     

The period prevalence of oral lichen planus in a cohort of patients with vulvar lichen sclerosus

Background Lichen sclerosus and lichen planus are chronic inflammatory mucocutaneous disorders that may coexist. Objective The aim of this study was to estimate the period prevalence of oral lichen planus in a cohort of patients with vulvar lichen sclerosus and to document their clinical characteristics. Methods We report a series of cases of vulvar lichen sclerosus presenting to two dermatologist‐led vulvar clinics in Oxfordshire, England between 1997 and 2007 with coexistent clinical signs of oral lichen planus. Results Thirteen cases with coexistent vulvar lichen sclerosus and oral lichen planus were identified, of which five had oral biopsies. Four oral biopsies showed histological features consistent with lichen planus. One oral biopsy was not diagnostic but compatible with oral lichen planus. No cases of oral lichen sclerosus were identified. The period prevalence of oral lichen planus was 6 per 1000 cases of vulvar lichen sclerosus. Conclusion The period prevalence of oral lichen planus in women with vulvar lichen sclerosus (0.6%) is similar to that reported for oral lichen planus in the general population (1–2%).     

Folliculotropic mycosis fungoides with eosinophilia and CD30+ large‐cell transformation: a case with a fatal outcome presenting with multifocal lesions and leonine facies

Eosinophilia is recognized as a poor prognostic factor in patients with cutaneous T‐cell lymphoma (CTCL). We report a case of folliculotropic mycosis fungoides (FMF) presenting with multiple ulcerative nodular lesions and persistent eosinophilia. Severe facial lesions resulted in a leonine appearance. On histopathological examination, nodular infiltration of large CD30+ large cells was seen. When the previous biopsy specimens were reviewed, marked folliculotropism with atypical lymphocytes was identified in previous specimens 20 years before the blastic transformation. CC chemokine receptor 3 was expressed in tumour cells, whereas CXC chemokine receptor 3 was negative. Expression of interleukin (IL)‐5 was detected in a few mononuclear lymphoid cells. This case demonstrates that T helper (Th)2‐polarized tumour cells may produce Th2 cytokines including IL‐5, which suggests that cytokines and chemokines may contribute to persistent eosinophilia and to recruitment of eosinophils into tumour lesions in advanced FMF.     

Necrotising herpetic retinopathy in patients with advance HIV disease.

OBJECTIVES: To describe the presenting features, clinical and laboratory diagnosis, response to treatment, and outcome of necrotising herpetic retinopathy (NHR) in HIV infected patients. METHODS: Retrospective case records/laboratory data review of five HIV infected patients presenting to the specialist HIV/AIDS unit at UCL Hospitals, London from April 1994 to August 1996 with a clinical diagnosis of NHR. RESULTS: All patients had advanced HIV disease with a median CD4 count of 20.10(6)/1. Three patients had cutaneous varicella zoster virus (VZV) infection within the preceding 8 weeks. All had uniocular loss of visual acuity; one also had headache and another ocular pain. All had typical retinal appearances. VZV DNA was detected in cerebrospinal fluid of four patients (and in vitreous fluid of one of the four) and in vitreous fluid of one other. One patient refused therapy and rapidly became blind. Four patients received intravenous foscarnet with intravenous aciclovir for 6 weeks: three subsequently received oral famciclovir and one oral valaciclovir; two patients also had intravitreal injections of foscarnet. In none of the four did treatment bring about improvement in visual acuity, but in all four visual loss from retinitis was halted. CONCLUSIONS: NHR occurs in HIV infected patients with advanced HIV disease and is strongly associated with evidence of VZV infection. With aggressive use of antiviral drugs the outcome is not uniformly poor.